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1. Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Author

Schettini, F, Blondeaux, E, Molinelli, C, Bas, R, Kim, H, Di Meglio, A, Bernstein Molho, R, Linn, S, Pogoda, K, Carrasco, E, Punie, K, Agostinetto, E, Lopetegui-Lia, N, Phillips, K, Toss, A, Rousset-Jablonski, C, Acheritogaray, M, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Dieci, M, Matikas, A, Rozenblit, M, Villarreal-Garza, C, De Marchis, L, Puglisi, F, Vasconcelos de Matos, L, Marino, M, Teixeira, L, Graffeo, R, Rognone, A, Chirco, A, Antone, N, Abdou, Y, Marhold, M, Bozovic-Spasojevic, I, Cortes Salgado, A, Carmisciano, L, Bruzzone, M, Curigliano, G, Prat, A, Lambertini, M, Schettini F., Blondeaux E., Molinelli C., Bas R., Kim H. J., Di Meglio A., Bernstein Molho R., Linn S. C., Pogoda K., Carrasco E., Punie K., Agostinetto E., Lopetegui-Lia N., Phillips K. -A., Toss A., Rousset-Jablonski C., Acheritogaray M., Ferrari A., Paluch-Shimon S., Fruscio R., Cui W., Wong S. M., Vernieri C., Dieci M. V., Matikas A., Rozenblit M., Villarreal-Garza C., De Marchis L., Puglisi F., Vasconcelos de Matos L., Marino M., Teixeira L., Graffeo R., Rognone A., Chirco A., Antone N., Abdou Y., Marhold M., Bozovic-Spasojevic I., Cortes Salgado A., Carmisciano L., Bruzzone M., Curigliano G., Prat A., Lambertini M., Schettini, F, Blondeaux, E, Molinelli, C, Bas, R, Kim, H, Di Meglio, A, Bernstein Molho, R, Linn, S, Pogoda, K, Carrasco, E, Punie, K, Agostinetto, E, Lopetegui-Lia, N, Phillips, K, Toss, A, Rousset-Jablonski, C, Acheritogaray, M, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Dieci, M, Matikas, A, Rozenblit, M, Villarreal-Garza, C, De Marchis, L, Puglisi, F, Vasconcelos de Matos, L, Marino, M, Teixeira, L, Graffeo, R, Rognone, A, Chirco, A, Antone, N, Abdou, Y, Marhold, M, Bozovic-Spasojevic, I, Cortes Salgado, A, Carmisciano, L, Bruzzone, M, Curigliano, G, Prat, A, Lambertini, M, Schettini F., Blondeaux E., Molinelli C., Bas R., Kim H. J., Di Meglio A., Bernstein Molho R., Linn S. C., Pogoda K., Carrasco E., Punie K., Agostinetto E., Lopetegui-Lia N., Phillips K. -A., Toss A., Rousset-Jablonski C., Acheritogaray M., Ferrari A., Paluch-Shimon S., Fruscio R., Cui W., Wong S. M., Vernieri C., Dieci M. V., Matikas A., Rozenblit M., Villarreal-Garza C., De Marchis L., Puglisi F., Vasconcelos de Matos L., Marino M., Teixeira L., Graffeo R., Rognone A., Chirco A., Antone N., Abdou Y., Marhold M., Bozovic-Spasojevic I., Cortes Salgado A., Carmisciano L., Bruzzone M., Curigliano G., Prat A., and Lambertini M.

Abstract

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤.05. Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p <.001), hormone receptor–positive (p <.001), and node-positive (p =.003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p <.001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2-low (p =.014) and TN and luminal A-like in HER2-0 (p =.019) showed the worst DFS. Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.

Published
2024

2. Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study

Author

Lambertini, M, Blondeaux, E, Agostinetto, E, Hamy, A, Kim, H, Di Meglio, A, Molho, R, Hilbers, F, Pogoda, K, Carrasco, E, Punie, K, Bajpai, J, Ignatiadis, M, Moore, H, Phillips, K, Toss, A, Rousset-Jablonski, C, Peccatori, F, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Ruddy, K, Dieci, M, Matikas, A, Rozenblit, M, Villarreal-Garza, C, De Marchis, L, Del Mastro, L, Puglisi, F, Estevez-Diz, M, Rodriguez-Wallberg, K, Mrinakova, B, Meister, S, Livraghi, L, Clatot, F, Yerushalmi, R, De Angelis, C, Sanchez-Bayona, R, Meattini, I, Cichowska-Cwalinska, N, Berliere, M, Salama, M, De Giorgi, U, Sonnenblick, A, Chiodi, C, Lee, Y, Maria, C, Azim, H, Boni, L, Partridge, A, Lambertini M., Blondeaux E., Agostinetto E., Hamy A. -S., Kim H. J., Di Meglio A., Molho R. B., Hilbers F., Pogoda K., Carrasco E., Punie K., Bajpai J., Ignatiadis M., Moore H. C. F., Phillips K. -A., Toss A., Rousset-Jablonski C., Peccatori F. A., Renaud T., Ferrari A., Paluch-Shimon S., Fruscio R., Cui W., Wong S. M., Vernieri C., Ruddy K. J., Dieci M. V., Matikas A., Rozenblit M., Villarreal-Garza C., De Marchis L., Del Mastro L., Puglisi F., Estevez-Diz M. D. P., Rodriguez-Wallberg K. A., Mrinakova B., Meister S., Livraghi L., Clatot F., Yerushalmi R., De Angelis C., Sanchez-Bayona R., Meattini I., Cichowska-Cwalinska N., Berliere M., Salama M., De Giorgi U., Sonnenblick A., Chiodi C., Lee Y. -J., Maria C., Azim H. A., Boni L., Partridge A. H., Lambertini, M, Blondeaux, E, Agostinetto, E, Hamy, A, Kim, H, Di Meglio, A, Molho, R, Hilbers, F, Pogoda, K, Carrasco, E, Punie, K, Bajpai, J, Ignatiadis, M, Moore, H, Phillips, K, Toss, A, Rousset-Jablonski, C, Peccatori, F, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Ruddy, K, Dieci, M, Matikas, A, Rozenblit, M, Villarreal-Garza, C, De Marchis, L, Del Mastro, L, Puglisi, F, Estevez-Diz, M, Rodriguez-Wallberg, K, Mrinakova, B, Meister, S, Livraghi, L, Clatot, F, Yerushalmi, R, De Angelis, C, Sanchez-Bayona, R, Meattini, I, Cichowska-Cwalinska, N, Berliere, M, Salama, M, De Giorgi, U, Sonnenblick, A, Chiodi, C, Lee, Y, Maria, C, Azim, H, Boni, L, Partridge, A, Lambertini M., Blondeaux E., Agostinetto E., Hamy A. -S., Kim H. J., Di Meglio A., Molho R. B., Hilbers F., Pogoda K., Carrasco E., Punie K., Bajpai J., Ignatiadis M., Moore H. C. F., Phillips K. -A., Toss A., Rousset-Jablonski C., Peccatori F. A., Renaud T., Ferrari A., Paluch-Shimon S., Fruscio R., Cui W., Wong S. M., Vernieri C., Ruddy K. J., Dieci M. V., Matikas A., Rozenblit M., Villarreal-Garza C., De Marchis L., Del Mastro L., Puglisi F., Estevez-Diz M. D. P., Rodriguez-Wallberg K. A., Mrinakova B., Meister S., Livraghi L., Clatot F., Yerushalmi R., De Angelis C., Sanchez-Bayona R., Meattini I., Cichowska-Cwalinska N., Berliere M., Salama M., De Giorgi U., Sonnenblick A., Chiodi C., Lee Y. -J., Maria C., Azim H. A., Boni L., and Partridge A. H.

Abstract

(Abstracted from JAMA 2024;331(1):49-59 Individuals who are diagnosed with breast cancer at a young age are often carriers of a pathogenic variant in the BRCA1 or BRCA2 genes, and many young women in this situation are interested in preserving future fertility, if possible. Reproductive counseling in this situation can be complex due to the risk of passing on the variant, as well as the implications on their own fertility, as the mutation can impact ovarian reserve, fertility potential, and other factors.

Published
2024

3. Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers

Author

Arecco, L, Bruzzone, M, Bas, R, Kim, H, Di Meglio, A, Bernstein-Molho, R, Hilbers, F, Pogoda, K, Carrasco, E, Punie, K, Bajpai, J, Agostinetto, E, Lopetegui-Lia, N, Partridge, A, Phillips, K, Toss, A, Rousset-Jablonski, C, Curigliano, G, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Couch, F, Dieci, M, Matikas, A, Rozenblit, M, Aguilar-y Mendez, D, De Marchis, L, Puglisi, F, Fabi, A, Graff, S, Witzel, I, Rodriguez Hernandez, A, Fontana, A, Pesce, R, Duchnowska, R, Pais, H, Sini, V, Sokolovic, E, de Azambuja, E, Ceppi, M, Blondeaux, E, Lambertini, M, Arecco L., Bruzzone M., Bas R., Kim H. J., Di Meglio A., Bernstein-Molho R., Hilbers F. S., Pogoda K., Carrasco E., Punie K., Bajpai J., Agostinetto E., Lopetegui-Lia N., Partridge A. H., Phillips K. A., Toss A., Rousset-Jablonski C., Curigliano G., Renaud T., Ferrari A., Paluch-Shimon S., Fruscio R., Cui W., Wong S. M., Vernieri C., Couch F. J., Dieci M. V., Matikas A., Rozenblit M., Aguilar-y Mendez D., De Marchis L., Puglisi F., Fabi A., Graff S. L., Witzel I., Rodriguez Hernandez A., Fontana A., Pesce R., Duchnowska R., Pais H. L., Sini V., Sokolovic E., de Azambuja E., Ceppi M., Blondeaux E., Lambertini M., Arecco, L, Bruzzone, M, Bas, R, Kim, H, Di Meglio, A, Bernstein-Molho, R, Hilbers, F, Pogoda, K, Carrasco, E, Punie, K, Bajpai, J, Agostinetto, E, Lopetegui-Lia, N, Partridge, A, Phillips, K, Toss, A, Rousset-Jablonski, C, Curigliano, G, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Couch, F, Dieci, M, Matikas, A, Rozenblit, M, Aguilar-y Mendez, D, De Marchis, L, Puglisi, F, Fabi, A, Graff, S, Witzel, I, Rodriguez Hernandez, A, Fontana, A, Pesce, R, Duchnowska, R, Pais, H, Sini, V, Sokolovic, E, de Azambuja, E, Ceppi, M, Blondeaux, E, Lambertini, M, Arecco L., Bruzzone M., Bas R., Kim H. J., Di Meglio A., Bernstein-Molho R., Hilbers F. S., Pogoda K., Carrasco E., Punie K., Bajpai J., Agostinetto E., Lopetegui-Lia N., Partridge A. H., Phillips K. A., Toss A., Rousset-Jablonski C., Curigliano G., Renaud T., Ferrari A., Paluch-Shimon S., Fruscio R., Cui W., Wong S. M., Vernieri C., Couch F. J., Dieci M. V., Matikas A., Rozenblit M., Aguilar-y Mendez D., De Marchis L., Puglisi F., Fabi A., Graff S. L., Witzel I., Rodriguez Hernandez A., Fontana A., Pesce R., Duchnowska R., Pais H. L., Sini V., Sokolovic E., de Azambuja E., Ceppi M., Blondeaux E., and Lambertini M.

Abstract

Background: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. Patients and methods: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. Results: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69

Published
2024

4. Characteristics and clinical outcomes of breast cancer in young BRCA carriers according to tumor histology

Author

Agostinetto, E, Bruzzone, M, Hamy, A, Kim, H, Chiodi, C, Bernstein-Molho, R, Linn, S, Pogoda, K, Carrasco, E, Derouane, F, Bajpai, J, Nader-Marta, G, Lopetegui-Lia, N, Partridge, A, Cortesi, L, Rousset-Jablonski, C, Giugliano, F, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Ruddy, K, Dieci, M, Matikas, A, Rozenblit, M, Aguilar Y Mendez, D, De Marchis, L, Borea, R, Puglisi, F, Pistelli, M, Kufel-Grabowska, J, Di Rocco, R, Mariamidze, E, Atzori, F, Kourie, H, Popovic, L, de Azambuja, E, Blondeaux, E, Lambertini, M, Hamy, A-S, Kim, H J, Partridge, A H, Wong, S M, Ruddy, K J, Dieci, M V, Kourie, H R, Agostinetto, E, Bruzzone, M, Hamy, A, Kim, H, Chiodi, C, Bernstein-Molho, R, Linn, S, Pogoda, K, Carrasco, E, Derouane, F, Bajpai, J, Nader-Marta, G, Lopetegui-Lia, N, Partridge, A, Cortesi, L, Rousset-Jablonski, C, Giugliano, F, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Ruddy, K, Dieci, M, Matikas, A, Rozenblit, M, Aguilar Y Mendez, D, De Marchis, L, Borea, R, Puglisi, F, Pistelli, M, Kufel-Grabowska, J, Di Rocco, R, Mariamidze, E, Atzori, F, Kourie, H, Popovic, L, de Azambuja, E, Blondeaux, E, Lambertini, M, Hamy, A-S, Kim, H J, Partridge, A H, Wong, S M, Ruddy, K J, Dieci, M V, and Kourie, H R

Abstract

Background: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer. Methods: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival. Results: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index. Conclusions: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis.

Published
2024

8. Optimizing choices and sequences in the diagnostic-therapeutic landscape of advanced triple-negative breast cancer: An Italian consensus paper and critical review

Author

Miglietta, F, Fabi, A, Generali, D, Dieci, M V, Arpino, G, Bianchini, G, Cinieri, S, Conte, P F, Curigliano, G, De Laurentis, M, Del Mastro, L, De Placido, S, Gennari, A, Puglisi, F, Zambelli, A, Perrone, F, and Guarneri, V

Subjects
Triple-negative breast cancer, Oncology, Radiology, Nuclear Medicine and imaging, General Medicine, Antibody-drug conjugate, Immune checkpoint-inhibitor, Metastatic breast cancer, PARP-inhibitor
Published
2023
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9. Risk and severity of SARS-CoV-2 infection in breast cancer patients undergoing a structured infection screening program at the University and Hospital Trust of Verona

Author

Zanelli, S, Fiorio, E, Zampiva, I, Zacchi, F, Borghesani, G, Giontella, E, Parolin, V, Biondani, P, Zuliani, S, Dieci, M V, Mioranza, E, Zorzi, M, Conti, M, Gibellini, D, Verlato, G, and Milella, M

Subjects
Universities, SARS-CoV-2, endocrine therapy, COVID-19, Breast Neoplasms, Hematology, Trust, chemotherapy, Hospitals, Breast cancer, Oncology, Humans, disease severity, Female, Early Detection of Cancer
Published
2022
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10. Survival after neoadjuvant therapy with trastuzumab-lapatinib and chemotherapy in patients with HER2-positive early breast cancer: a meta-analysis of randomized trials

Author

Guarneri, V, Griguolo, G, Miglietta, F, Conte, P F, Dieci, M V, and Girardi, F

Subjects
neoadjuvant treatment, Receptor, ErbB-2, Breast Neoplasms, Lapatinib, Trastuzumab, Hormones, Neoadjuvant Therapy, meta-analysis, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Neoplasm Recurrence, Local, HER2-positive breast cancer, HER2-positive breast cancer, neoadjuvant treatment, lapatinib, trastuzumab, meta-analysis, Randomized Controlled Trials as Topic
Abstract

Studies testing the addition of lapatinib to neoadjuvant trastuzumab + chemotherapy reported an increase in pathologic complete response (pCR), with, nevertheless, discordant results in terms of survival, mainly due to suboptimal power. We here leverage the meta-analytic approach to resolve these inconsistencies.We conducted a meta-analysis of randomized phase II/III studies testing lapatinib + trastuzumab in combination with neoadjuvant chemotherapy for human epidermal growth factor receptor (HER2)-positive early breast cancer (BC). Recurrence-free survival (RFS) and overall survival (OS) were adopted as survival endpoints. Pooled hazard ratios (HR) were obtained for the effect of lapatinib + trastuzumab versus trastuzumab, pCR versus no-pCR in the whole study populations and pCR versus no-pCR according to hormone receptor status.Four phase II/III randomized trials were included in the meta-analysis (CALGB 40601, Cher-LOB, NSABP-B41, NeoALTTO) for an overall population of 1410 patients receiving neoadjuvant chemotherapy in association with either trastuzumab, lapatinib or their combination. RFS was significantly improved with dual HER2 blockade as compared to trastuzumab [HR 0.62, 95% confidence interval (CI) 0.46-0.85]. Dual blockade also led to significantly improved OS (HR 0.65, 95% CI 0.43-0.98). For all treatments combined, patients achieving pCR had better RFS and OS than those with residual disease (HR 0.45, 95% CI 0.34-0.60, and HR 0.32, 95% CI 0.22-0.48, for RFS and OS, respectively). In patients with hormone receptor-negative tumors, pCR was associated with 65% and 73% relative reduction of risk of relapse and death, respectively. Patients with hormone receptor-positive tumors also experienced improved RFS if they achieved pCR; however, the benefit was smaller than that in hormone receptor-negative disease.Findings from this meta-analysis further validate the role of pCR as a strong predictor of outcome in patients with HER2-positive BC, especially in hormone receptor-negative disease. Moreover, we provide robust evidence that dual blockade with lapatinib + trastuzumab in combination with neoadjuvant chemotherapy prolongs OS, suggesting that the role of lapatinib could be reconsidered in the early setting.

Published
2021

11. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Author

El Bairi, K., Haynes, H. R., Blackley, E., Fineberg, S., Shear, J., Turner, S., de Freitas, J. R., Sur, D., Amendola, L. C., Gharib, M., Kallala, A., Arun, I., Azmoudeh-Ardalan, F., Fujimoto, L., Sua, L. F., Liu, S. -W., Lien, H. -C., Kirtani, P., Balancin, M., El Attar, H., Guleria, P., Yang, W., Shash, E., Chen, I. -C., Bautista, V., Do Prado Moura, J. F., Rapoport, B. L., Castaneda, C., Spengler, E., Acosta-Haab, G., Frahm, I., Sanchez, J., Castillo, M., Bouchmaa, N., Md Zin, R. R., Shui, R., Onyuma, T., Husain, Z., Willard-Gallo, K., Coosemans, A., Perez, E. A., Provenzano, E., Ericsson, P. G., Richardet, E., Mehrotra, R., Sarancone, S., Ehinger, A., Rimm, D. L., Bartlett, J. M. S., Viale, G., Denkert, C., Hida, A. I., Sotiriou, C., Loibl, S., Hewitt, S. M., Badve, S., Symmans, W. F., Kim, R. S., Pruneri, G., Goel, S., Francis, P. A., Inurrigarro, G., Yamaguchi, R., Garcia-Rivello, H., Horlings, H., Afqir, S., Salgado, R., Adams, S., Kok, M., Dieci, M. V., Michiels, S., Demaria, S., Loi, S., Schelfhout, V., Arbzadeh, E., Bondanar, A., Reyes, S. A. G., Ruz, J. R., Kang, J., Xiang, L., Zimovjanova, M., Togores, P., Ozturk, T., Patil, A., Corpa, M., Whitehouse, A., Tan, B., de Paula, A., Rossetti, C., Lang-Schwarz, C., Mahon, S., Giacometti, C., Linderholm, B., Deman, F., Montagna, G., Gong, G., Pavcovich, M., Chaer, Y., Cabrero, I. A., de Brito, M. L., Ilieva, N., Fulop, A., Souza, M., Bilancia, D., Idowu, M., Johri, R., Szpor, J., Bachani, L., Schmitt, F., Giannotti, M., Kurebayashi, Y., Ramirez, B. E. A., Salido, E., Bortesi, L., Bonetto, S., Elomina, K., Lopez, P., Sharma, V., Edirisinghe, A., Mathur, D., Sahay, A., Mouloud, M. A., Giang, C. H., Mukolwe, E., Kiruka, E., Samberg, N., Abe, N., Brown, M., Millar, E., X. B., Li, Yuan, Z., Pasupathy, A., Miele, R., Luff, R., e Porfirio, M. M. A., Ajemba, O., Soni, R., Orvieto, E., Dimaio, M., Thomas, J., Merard, R., Subramaniam, M. M., Apolinario, T., Preda, O., Preda, R., Makanga, A., Maior, M. S., Li, L., Saghatchian, M., Saurine, T., Janssen, E., Cochran, J., Vlada, N., Cappellesso, R., Elfer, K., Hollick, M., Desai, S., Oner, G., Schreurs, A., Liu, S., Perera, R., Mercurio, P., Garcia, F., Hosny, K., Matsumoto, H., van Deurzen, C., Bianchini, G., Coban, I., Jahangir, A., Rahman, A., Stover, D., Luz, P., Martel, A., Waumans, Y., Stenzinger, A., Cortes, J., Dimitrova, P., Nauwelaers, I., Velasco, M., Fan, F., Akturk, G., Firer, M., Roxanis, I., Schneck, M., Wen, H., Cockenpot, V., Konstantinov, A., Calatrava, A., Vidya, M. N., Choi, H. J., Jank, P., Ciinen, A. H., Sabanathan, D., Floris, G., Hoeflmayer, D., Hamada, T., Laudus, N., Grigoriadis, A., Porcellato, I., Acs, B., Miglietta, F., Parrodi, J., Clunie, D., Calhoun, B., F. -I., Lu, Lefevre, A., Tabbarah, S., Tran, W., Garcia-murillas, I., Jelinic, P., Boeckx, C., Souza, S., Cebollero, M. C., Felip, E., Rendon, J. L. S., El Gabry, E., Saltz, J., Bria, E., Garufi, G., Hartman, J., Sebastian, M., Olofsson, H., Kooreman, L., Cucherousset, J., Mathieu, M. -C., Ballesteros-Merino, C., Siziopikou, P., Fong, J., Klein, M., Qulis, I. R. I., Wesseling, J., Bellolio, E., Araya, J. C., Naber, S., Cheang, M., Castellano, I., Ales, A., Laenkholm, A. -V., Kulka, J., Quinn, C., Sapino, A., Amendoeira, I., Marchio, C., Braybrooke, J., Vincent-Salomon, A., Korski, K. P., Sofopoulos, M., Stovgaard, E. I. S., Bianchi, S., Bago-Horvath, Z., Yu, C., Regitnig, P., Hall, S., Kos, Z., Sant, S., Tille, J. -C., Gallas, B., Bethmann, D., Savas, P., Mendes, L., Soler, T., van Seijen, M., Gruosso, T., Quintana, A., Giltnane, J., Van den Eynden, G., Duregon, E., de Cabo, R., Recamo, P. C., Gaboury, L., Zimmerman, J., Pop, C. S., Wernicke, A., Williams, D., Gill, A., Solomon, B., Thapa, B., Farshid, G., Gilham, L., Christie, M., O'Toole, S., Hendry, S., Fox, S. B., Luen, S. J., Lakhani, S. R., Fuchs, T., John, T., Brcic, I., Hainfellner, J., Sigurd, L., Preusser, M., Poortmans, P., Decaluwe, A., Carey, C., Colpaert, C., Larsimont, D., Peeters, D., Broeckx, G., van de Vijver, K., Buisseret, L., Dirix, L., Hertoghs, M., Piccart, M., Ignatiadis, M., Van Bockstal, M., Sirtaine, N., Vermeulen, P., de Wind, R., Declercq, S., Gevaert, T., Haibe-Kans, B., Nelson, B. H., Watson, P. H., Leung, S., Nielsen, T., Shi, L., Balslev, E., Thagaard, J., Almangush, A., Makitie, A., Joensuu, H., Lundin, J., Drubay, D., Roblin, E., Andre, F., Penault-Llorca, F., Lemonnier, J., Adam, J., Lacroix-Triki, M., Ternes, N., Radosevic-Robin, N., Klaushen, F., Weber, K., Harbeck, N., Gluz, O., Wienert, S., Cserni, G., Vingiani, A., Criscitiello, C., Solinas, C., Curigliano, G., Konishi, E., Suzuki, E., Yoshikawa, K., Kawaguchi, K., Takada, M., Toi, M., Ishida, M., Shibata, N., Saji, S., Kogawa, T., Sakatani, T., Okamoto, T., Moriya, T., Kataoka, T., Shimoi, T., Sugie, T., Mukohara, T., Shu, Y., Kikawa, Y., Kozuka, Y., Sayed, S., Rahayu, R., Ramsaroop, R., Senkus-Konefka, E., Chmielik, E., Cardoso, F., Ribeiro, J., Chan, J., Dent, R., Martin, M., Hagen, C., Guerrero, A., Rojo, F., Comerma, L., Nuciforo, P., Serrano, V. V., Camaea, V. P., Steenbruggen, T., Ciompi, F., Nederlof, I., Jan, Hudecek, van der Laak, J., van den Berg, J., Voorwerk, L., van de Vijver, M., de Maaker, M., Linn, S., Mckenzie, H., Somaiah, N., Tutt, A., Swanton, C., Hiley, C., Moore, D. A., Hall, J. A., Le Quesne, J., Jabbar, K. A., al Bakir, M., Hills, R., Irshad, S., Yuan, Y., Li, Z., Liu, M., Klein, J., Fadare, O., Thompson, A., Lazar, A. J., Gown, A., Lo, A., Garrido Castro, A. C., Madabhushi, A., Moreira, A., Richardson, A., Beck, A. H., Bellizzi, A. M., Wolff, A., Harbhajanka, A., Sharma, A., Cimino-Mathews, A., Srinivasan, A., Singh, B., Chennubhotla, C. S., Chauhan, C., Dillon, D. A., Zardavas, D., Johnson, D. B., Thompson, A. E., Brogi, E., Reisenbichler, E., Huang, E., Hirsch, F. R., Mcarthur, H., Ziai, J., Brock, J., Kerner, J., Zha, J., Lennerz, J. K., Carter, J. M., Reis-Filho, J., Sparano, J., Balko, J. M., Pogue-Geile, K., Steele, K. E., Blenman, K. R. M., Allison, K. H., Pusztai, L., Cooper, L., Estrada, V. M., Flowers, M., Robson, M., Rebelatto, M. C., Hanna, M. G., Goetz, M. P., Khojasteh, M., Sanders, M. E., Regan, M. M., Misialek, M., Amgad, M., Tung, N., Singh, R., Huang, R., Pierce, R. H., Leon-Ferre, R., Swain, S., Ely, S., Kim, S. -R., Bedri, S., Paik, S., Schnitt, S., D'Alfons, T., Kurkure, U., Bossuyt, V., Tong, W., Wang, Y., Dos Anjos, C. H., Gaire, F., Van Diest, P. J., El Bairi, Khalid [0000-0002-8414-4145], de Freitas, Juliana Ribeiro [0000-0003-4978-7273], Sur, Daniel [0000-0002-0926-4614], Amendola, Luis Claudio [0000-0002-6404-450X], Azmoudeh-Ardalan, Farid [0000-0003-4701-0532], Kirtani, Pawan [0000-0002-2343-7016], Yang, Wenxian [0000-0002-5349-9680], Castillo, Miluska [0000-0002-0111-3176], Provenzano, Elena [0000-0003-3345-3965], Mehrotra, Ravi [0000-0001-9453-1408], Ehinger, Anna [0000-0001-9225-7396], Rimm, David L [0000-0001-5820-4397], Bartlett, John MS [0000-0002-0347-3888], Denkert, Carsten [0000-0002-2249-0982], Hida, Akira I [0000-0002-4486-8819], Sotiriou, Christos [0000-0002-5745-9977], Hewitt, Stephen M [0000-0001-8283-1788], Badve, Sunil [0000-0001-8861-9980], Symmans, William Fraser [0000-0002-1526-184X], Goel, Shom [0000-0001-8329-9084], Francis, Prudence A [0000-0002-7207-9286], Horlings, Hugo [0000-0003-4782-8828], Salgado, Roberto [0000-0002-1110-3801], Demaria, Sandra [0000-0003-4426-0499], Loi, Sherene [0000-0001-6137-9171], Apollo - University of Cambridge Repository, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), and UNICANCER

Subjects
Oncology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], TRASTUZUMAB, Improved survival, MICROENVIRONMENT, Review Article, SUBTYPES, NEOADJUVANT CHEMOTHERAPY, 0302 clinical medicine, Breast cancer, Ecology,Evolution & Ethology, PROGNOSTIC-SIGNIFICANCE, Medicine and Health Sciences, Pharmacology (medical), TUMOR-INFILTRATING LYMPHOCYTES, Stage (cooking), RC254-282, Chemical Biology & High Throughput, 0303 health sciences, Human Biology & Physiology, Genome Integrity & Repair, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ASSOCIATION, 3. Good health, 030220 oncology & carcinogenesis, Biomarker (medicine), Life Sciences & Biomedicine, Genetics & Genomics, medicine.medical_specialty, chemical and pharmacologic phenomena, International Immuno-Oncology Biomarker Working Group, Predictive markers, 03 medical and health sciences, Signalling & Oncogenes, SDG 3 - Good Health and Well-being, Internal medicine, 692/53/2423, medicine, Radiology, Nuclear Medicine and imaging, In patient, 030304 developmental biology, Computational & Systems Biology, Science & Technology, IDENTIFICATION, business.industry, review-article, Cancer, 03.01. Általános orvostudomány, Immunotherapy, Tumour Biology, medicine.disease, PREDICTIVE-VALUE, 692/4028/67/1347, Programmed death 1, business, FREE SURVIVAL
Abstract

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC. ispartof: NPJ BREAST CANCER vol:7 issue:1 ispartof: location:United States status: published

Published
2021
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13. Immune Infiltrates in Breast Cancer: Recent Updates and Clinical Implications

Author

Dieci, M. V., Miglietta, F., and Guarneri, V.

Subjects
PD-L1, Clinical Trials as Topic, Lymphoid Tissue, Immunity, chemical and pharmacologic phenomena, Breast Neoplasms, Review, breast cancer, immune biomarker, immune infiltrate, immunotherapy, tumor-infiltrating lymphocytes, lcsh:Biology (General), Tumor Microenvironment, Humans, Female, Lymphocytes, lcsh:QH301-705.5
Abstract

In recent decades, the increasing interest in the field of immunotherapy has fostered an intense investigation of the breast cancer (BC) immune microenvironment. In this context, tumor-infiltrating lymphocytes (TILs) have emerged as a clinically relevant and highly reproducible biomarker capable of affecting BC prognosis and response to treatment. Indeed, the evaluation of TILs on primary tumors proved to be strongly prognostic in triple-negative (TN) BC patients treated with either adjuvant or neoadjuvant chemotherapy, as well as in early TNBC patients not receiving any systemic treatment, thus gaining level-1b evidence in this setting. In addition, a strong relationship between TILs and pathologic complete response after neoadjuvant chemotherapy has been reported in all BC subtypes and the prognostic role of higher TILs in early HER2-positive breast cancer patients has also been demonstrated. The interest in BC immune infiltrates has been further fueled by the introduction of the first immune checkpoint inhibitors in the treatment armamentarium of advanced TNBC in patients with PD-L1-positive status by FDA-approved assays. However, despite these advances, a biomarker capable of reliably and exhaustively predicting immunotherapy benefit in BC is still lacking, highlighting the imperative need to further deepen this issue. Finally, more comprehensive evaluation of immune infiltrates integrating both the quantity and quality of tumor-infiltrating immune cells and incorporation of TILs in composite scores encompassing other clinically or biologically relevant biomarkers, as well as the adoption of software-based and/or machine learning platforms for a more comprehensive characterization of BC immune infiltrates, are emerging as promising strategies potentially capable of optimizing patient selection and stratification in the research field. In the present review, we summarize available evidence and recent updates on immune infiltrates in BC, focusing on current clinical applications, potential clinical implications and major unresolved issues.

Published
2021

14. Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Condorelli, M, Bruzzone, M, Ceppi, M, Ferrari, A, Grinshpun, A, Hamy, A S, de Azambuja, E, Carrasco, E, Peccatori, F A, Di Meglio, A, Paluch-Shimon, S, Poorvu, P D, Venturelli, M, Rousset-Jablonski, C, Senechal, C, Livraghi, L, Ponzone, R, De Marchis, L, Pogoda, K, Sonnenblick, A, Villarreal-Garza, C, Córdoba, O, Teixeira, L, Clatot, F, Punie, K, Graffeo, R, Dieci, M V, Pérez-Fidalgo, J A, Duhoux, Francois, Puglisi, F, Ferreira, A R, Blondeaux, E, Peretz-Yablonski, T, Caron, O, Saule, C, Ameye, L, Balmaña, J, Partridge, A H, Azim, H A, Demeestere, I, Lambertini, M, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Condorelli, M, Bruzzone, M, Ceppi, M, Ferrari, A, Grinshpun, A, Hamy, A S, de Azambuja, E, Carrasco, E, Peccatori, F A, Di Meglio, A, Paluch-Shimon, S, Poorvu, P D, Venturelli, M, Rousset-Jablonski, C, Senechal, C, Livraghi, L, Ponzone, R, De Marchis, L, Pogoda, K, Sonnenblick, A, Villarreal-Garza, C, Córdoba, O, Teixeira, L, Clatot, F, Punie, K, Graffeo, R, Dieci, M V, Pérez-Fidalgo, J A, Duhoux, Francois, Puglisi, F, Ferreira, A R, Blondeaux, E, Peretz-Yablonski, T, Caron, O, Saule, C, Ameye, L, Balmaña, J, Partridge, A H, Azim, H A, Demeestere, I, and Lambertini, M

Abstract

Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testi

Published
2021

17. Synchronous and Metachronous Breast and Ovarian Cancer: Experience From Two Large Cancer Center

Author

Tasca, G., Dieci, M. V., Baretta, Z., Faggioni, G., Montagna, M., Nicoletto, M. O., Peccatori, F. A., Guarneri, V., Colombo, N., Tasca, G, Dieci, M, Baretta, Z, Faggioni, G, Montagna, M, Nicoletto, M, Peccatori, F, Guarneri, V, and Colombo, N

Subjects
breast cancer, ovarian cancer, Oncology, metachronous cancer, BRCA mutation, doublet tumors, doublet tumor, synchronous cancer, Original Research
Abstract

Purpose: We aimed to evaluate the clinico-pathological characteristics and survival outcomes of patients with synchronous or metachronous breast cancer (BC) and ovarian cancer (OC). Materials and Methods: Patients with synchronous or metachronous BC and OC were retrospectively identified at two large cancer centers. Clinico-pathological characteristics, BRCA1/2 status and follow-up data were gathered. Patients were classified according to the first cancer diagnosis in the following groups: Breast Cancer first, Ovarian Cancer first, Synchronous Breast and Ovarian Cancer. Overall survival (OS) was calculated as the time interval between each cancer diagnosis to death or last follow-up. Results: Overall, 270 patients were included: n = 194 (72%) in BC first group, n = 51 (19%) in OC first, and n = 25 (9%) in synchronous. BRCA status was available for 182 (67.4%) patients and 112 (62%) harbored pathogenetic mutations. BC first group included more frequently patients with BRCA mutation, triple negative BC phenotype and more aggressive OC features. Median time between the two diagnosis was longer in BC first group vs OC first group (95 vs 68 months, p = 0.021). A total of 105 OS events occurred, mostly related to OC (70.5%). We observed no differences in terms of OS according to the first cancer diagnosis. Age >50 years and advanced OC stage were negative independent prognostic factors for OS from the first diagnosis. Conclusions: In this cohort of patients with BC and OC, survival was dominated by OC related mortality. These data may be useful to plan and carry out adequate and timely surveillance programs and preventive measures.

Published
2020

18. Biomarkers for HER2-positive metastatic breast cancer: Beyond hormone receptors

Author

Dieci, M. V., Miglietta, F., Griguolo, G., and Guarneri, V.

Subjects
Tumor, Receptor, ErbB-3, Receptor, ErbB-2, Breast Neoplasms, Receptors, Cell Surface, Metastatic breast cancer, Targeted therapy, ErbB-2, ErbB-3, Receptors, Cell Surface, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Humans, Female, Neoplasm Metastasis, HER2-positive breast cancer, Biomarkers, Randomized Controlled Trials as Topic, Receptor
Abstract

The overexpression of human epidermal growth factor receptor-2 (HER2) results in a biologically and clinically aggressive breast cancer (BC) subtype. Since the introduction of anti-HER2 targeted agents, survival rates of patients with HER2-positive metastatic BC have dramatically improved. Currently, although the treatment decision process in metastatic BC is primarily based on HER2 and hormone-receptor (HR) status, a rapidly growing body of data suggests that several other sources of biological heterogeneity may characterize HER2-positive metastatic BC. Moreover, pivotal clinical trials of new anti-HER2 antibody-drug conjugates showed encouraging results in HER2-low metastatic BC, thus leading to the possibility, in the near future, to expand the pool of patients suitable for HER2-targeted treatments. The present review summarizes and puts in perspective available evidence on biomarkers that hold the greatest promise to become potentially useful tools for optimizing HER2-positive metastatic BC patients' prognostic stratification and treatment in the next future. These biomarkers include HER2 levels and heterogeneity, HER3, intrinsic molecular subtypes by PAM50 analysis, DNA mutations, and immune-related factors. Molecular discordance between primary and metastatic tumors is also discussed.

Published
2020

19. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Author

Kos, Z., Roblin, E., Kim, R. S., Michiels, S., Gallas, B. D., Chen, W., van de Vijver, K. K., Goel, S., Adams, S., Demaria, S., Viale, G., Nielsen, T. O., Badve, S. S., Symmans, W. F., Sotiriou, C., Rimm, D. L., Hewitt, S., Denkert, C., Loibl, S., Luen, S. J., Bartlett, J. M. S., Savas, P., Pruneri, G., Dillon, D. A., Cheang, M. C. U., Tutt, A., Hall, J. A., Kok, M., Horlings, H. M., Madabhushi, A., van der Laak, J., Ciompi, F., Laenkholm, A. -V., Bellolio, E., Gruosso, T., Fox, S. B., Araya, J. C., Floris, G., Hudecek, J., Voorwerk, L., Beck, A. H., Kerner, J., Larsimont, D., Declercq, S., Van den Eynden, G., Pusztai, L., Ehinger, A., Yang, W., Abduljabbar, K., Yuan, Y., Singh, R., Hiley, C., Bakir, M., Lazar, A. J., Naber, S., Wienert, S., Castillo, M., Curigliano, G., Dieci, M. -V., Andre, F., Swanton, C., Reis-Filho, J., Sparano, J., Balslev, E., Chen, I. -C., Stovgaard, E. I. S., Pogue-Geile, K., Blenman, K. R. M., Penault-Llorca, F., Schnitt, S., Lakhani, S. R., Vincent-Salomon, A., Rojo, F., Braybrooke, J. P., Hanna, M. G., Soler-Monso, M. T., Bethmann, D., Castaneda, C. A., Willard-Gallo, K., Sharma, A., Lien, H. -C., Fineberg, S., Thagaard, J., Comerma, L., Gonzalez-Ericsson, P., Brogi, E., Loi, S., Saltz, J., Klaushen, F., Cooper, L., Amgad, M., Moore, D. A., Salgado, R., Hyytiainen, A., Hida, A. I., Thompson, A., Lefevre, A., Gown, A., Lo, A., Sapino, A., Moreira, A. M., Richardson, A., Vingiani, A., Bellizzi, A. M., Guerrero, A., Grigoriadis, A., Garrido-Castro, A. C., Cimino-Mathews, A., Srinivasan, A., Acs, B., Singh, B., Calhoun, B., Haibe-Kans, B., Solomon, B., Thapa, B., Nelson, B. H., Ballesteroes-Merino, C., Criscitiello, C., Boeckx, C., Colpaert, C., Quinn, C., Chennubhotla, C. S., Solinas, C., Drubay, D., Sabanathan, D., Peeters, D., Zardavas, D., Hoflmayer, D., Johnson, D. B., Thompson, E. A., Perez, E., Elgabry, E. A., Blackley, E. F., Reisenbichler, E., Chmielik, E., Gaire, F., F. -I., Lu, Azmoudeh-Ardalan, F., Peale, F., Hirsch, F. R., Acosta-Haab, G., Farshid, G., Broeckx, G., Koeppen, H., Haynes, H. R., Mcarthur, H., Joensuu, H., Olofsson, H., Cree, I., Nederlof, I., Frahm, I., Brcic, I., Chan, J., Ziai, J., Brock, J., Weseling, J., Giltnane, J., Lemonnier, J., Zha, J., Ribeiro, J., Lennerz, J. K., Carter, J. M., Hartman, J., Hainfellner, J., Le Quesne, J., Juco, J. W., van den Berg, J., Sanchez, J., Cucherousset, J., Adam, J., Balko, J. M., Saeger, K., Siziopikou, K., Sikorska, K., Weber, K., Steele, K. E., Emancipator, K., El Bairi, K., Allison, K. H., Korski, K., Buisseret, L., Shi, L., Kooreman, L. F. S., Molinero, L., Estrada, M. V., Van Seijen, M., Lacroix-Triki, M., Sebastian, M. M., Balancin, M. L., Mathieu, M. -C., van de Vijver, M., Rebelatto, M. C., Piccart, M., Goetz, M. P., Preusser, M., Khojasteh, M., Sanders, M. E., Regan, M. M., Barnes, M., Christie, M., Misialek, M., Ignatiadis, M., de Maaker, M., Van Bockstal, M., Harbeck, N., Tung, N., Laudus, N., Sirtaine, N., Burchardi, N., Ternes, N., Radosevic-Robin, N., Gluz, O., Grimm, O., Nuciforo, P., Jank, P., Kirtani, P., Watson, P. H., Jelinic, P., Francis, P. A., Russell, P. A., Pierce, R. H., Hills, R., Leon-Ferre, R., de Wind, R., Shui, R., Leung, S., Tabbarah, S., Souza, S. C., O'Toole, S., Swain, S., Dudgeon, S., Willis, S., Ely, S., Bedri, S., Irshad, S., Liu, S., Hendry, S., Bianchi, S., Braganca, S., Paik, S., Luz, S., Gevaert, T., D'Alfons, T., John, T., Sugie, T., Kurkure, U., Bossuyt, V., Manem, V., Camaea, V. P., Tong, W., Tran, W. T., Wang, Y., Allory, Y., Husain, Z., Bago-Horvath, Z., Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Division of Pathology and Laboratory Medicine, Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Charité, Institute of Pathology, Translational Tumorpathology Unit, German Breast Group, University of the Sunshine Coast (USC), European Institute of Oncology [Milan] (ESMO), Breakthrough Breast Cancer Centre, London Institute of Cancer, Department of Pathology, The Netherlands Cancer Institute, Division of Experimental Therapy, The Netherlands Cancer Institute NKI/AvL, Odense University Hospital, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Breast Medical Oncology [Houston], The University of Texas M.D. Anderson Cancer Center [Houston], Helsingborg Hospital, Division of Experimental Therapeutics [Milan, Italy], Département de médecine oncologique [Gustave Roussy], Cancer Research UK Lung Cancer Centre of Excellence [Londres, Royaume-Uni], University College of London [London] (UCL), Memorial Sloane Kettering Cancer Center [New York], Herlev and Gentofte Hospital, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Southern Queensland (USQ), Pharmacogenomics Unit [Paris], Department of Genetics [Paris], Institut Curie [Paris]-Institut Curie [Paris], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Ctr Biomol Struct & Org, University of Maryland [College Park], University of Maryland System-University of Maryland System, The University of Sydney, Breast Cancer Translational Research Laboratory, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Innovation North - Faculty of Information and Technology, Leeds Metropolitan University, Int Immuno-Oncology Biomarker, Graduate School, CCA - Cancer biology and immunology, Pathology, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), German Breast Group (GBG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Gallas, Brandon D [0000-0001-7332-1620], van de Vijver, Koen K [0000-0002-2026-9790], Demaria, Sandra [0000-0003-4426-0499], Badve, Sunil S [0000-0001-8861-9980], Symmans, W Fraser [0000-0002-1526-184X], Rimm, David L [0000-0001-5820-4397], Savas, Peter [0000-0001-5999-428X], Hall, Jacqueline A [0000-0003-0708-1360], Horlings, Hugo M [0000-0003-4782-8828], van der Laak, Jeroen [0000-0001-7982-0754], Bellolio, Enrique [0000-0003-0079-5264], Araya, Juan Carlos [0000-0003-3501-8203], Floris, Giuseppe [0000-0003-2391-5425], Hudeček, Jan [0000-0003-1071-5686], Ehinger, Anna [0000-0001-9225-7396], Lazar, Alexander J [0000-0002-6395-4499], Castillo, Miluska [0000-0002-0111-3176], Curigliano, Giuseppe [0000-0003-1781-2518], Sparano, Joseph [0000-0002-9031-2010], Braybrooke, Jeremy P [0000-0003-1943-7360], Hanna, Matthew G [0000-0002-7536-1746], Willard-Gallo, Karen [0000-0002-1150-1295], Sharma, Ashish [0000-0002-1011-6504], Comerma, Laura [0000-0002-0249-4636], Gonzalez-Ericsson, Paula [0000-0002-6292-6963], Loi, Sherene [0000-0001-6137-9171], Cooper, Lee [0000-0002-3504-4965], Apollo - University of Cambridge Repository, Research Programs Unit, Heikki Joensuu / Principal Investigator, HUS Comprehensive Cancer Center, Department of Oncology, Medicum, Gallas, Brandon D. [0000-0001-7332-1620], van de Vijver, Koen K. [0000-0002-2026-9790], Badve, Sunil S. [0000-0001-8861-9980], Symmans, W. Fraser [0000-0002-1526-184X], Rimm, David L. [0000-0001-5820-4397], Hall, Jacqueline A. [0000-0003-0708-1360], Horlings, Hugo M. [0000-0003-4782-8828], Lazar, Alexander J. [0000-0002-6395-4499], Braybrooke, Jeremy P. [0000-0003-1943-7360], and Hanna, Matthew G. [0000-0002-7536-1746]

Subjects
Oncology, [SDV]Life Sciences [q-bio], THERAPY, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Prognostic markers, 0302 clinical medicine, Breast cancer, Medicine and Health Sciences, Pharmacology (medical), Lymphocytes, Stromal tumor, health care economics and organizations, 0303 health sciences, CHEMOTHERAPY, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], PROGNOSTIC VALUE, Clinical Practice, 030220 oncology & carcinogenesis, Educational resources, Immunosurveillance, medicine.medical_specialty, 3122 Cancers, [SDV.CAN]Life Sciences [q-bio]/Cancer, IMMUNITY, lcsh:RC254-282, Article, Limfòcits, Càncer de mama, 03 medical and health sciences, Gastrointestinal cancer, SDG 3 - Good Health and Well-being, Internal medicine, 692/53/2422, medicine, Radiology, Nuclear Medicine and imaging, Càncer gastrointestinal, 030304 developmental biology, Predictive biomarker, Tumor-infiltrating lymphocytes, business.industry, Médecine pathologie humaine, medicine.disease, Cancérologie, Human medicine, business, SYSTEM, 631/67/580/1884
Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls., info:eu-repo/semantics/published

Published
2020
Full Text
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20. Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Author

Hudecek, J., Voorwerk, L., van Seijen, M., Nederlof, I., de Maaker, M., van den Berg, J., van de Vijver, K. K., Sikorska, K., Adams, S., Demaria, S., Viale, G., Nielsen, T. O., Badve, S. S., Michiels, S., Symmans, W. F., Sotiriou, C., Rimm, D. L., Hewitt, S. M., Denkert, C., Loibl, S., Loi, S., Bartlett, J. M. S., Pruneri, G., Dillon, D. A., Cheang, M. C. U., Tutt, A., Hall, J. A., Kos, Z., Salgado, R., Kok, M., Horlings, H. M., Hyytiainen, A., Hida, A. I., Thompson, A., Lefevre, A., Lazar, A. J., Gown, A., Lo, A., Sapino, A., Madabhushi, A., Moreira, A., Richardson, A., Vingiani, A., Beck, A. H., Bellizzi, A. M., Guerrero, A., Grigoriadis, A., Ehinger, A., Garrido-Castro, A., Vincent-Salomon, A., Laenkholm, A. -V., Sharma, A., Cimino-Mathews, A., Srinivasan, A., Acs, B., Singh, B., Calhoun, B., Haibe-Kans, B., Solomon, B., Thapa, B., Nelson, B. H., Gallas, B. D., Castaneda, C., Ballesteros-Merino, C., Criscitiello, C., Boeckx, C., Colpaert, C., Quinn, C., Chennubhotla, C. S., Swanton, C., Solinas, C., Hiley, C., Drubay, D., Bethmann, D., Moore, D. A., Larsimont, D., Sabanathan, D., Peeters, D., Zardavas, D., Hoflmayer, D., Johnson, D. B., Thompson, E. A., Brogi, E., Perez, E., Elgabry, E. A., Stovgaard, E. S., Blackley, E. F., Roblin, E., Reisenbichler, E., Bellolio, E., Balslev, E., Chmielik, E., Gaire, F., Andre, F., F. -I., Lu, Azmoudeh-Ardalan, F., Rojo, F., Gruosso, T., Ciompi, F., Peale, F., Hirsch, F. R., Klauschen, F., Penault-Llorca, F., Acosta Haab, G., Farshid, G., van den Eynden, G., Curigliano, G., Floris, G., Broeckx, G., Gonzalez-Ericsson, Koeppen, H., Haynes, H. R., Mcarthur, H., Joensuu, H., Olofsson, H., Lien, H. -C., Chen, I. -C., Cree, I., Frahm, I., Brcic, I., Chan, J., Ziai, J., Brock, J., Wesseling, J., Giltnane, J., Kerner, J. K., Thagaard, J., Braybrooke, J. P., van der Laak, J. A. W. M., Lemonnier, J., Zha, J., Ribeiro, J., Lennerz, J. K., Carter, J. M., Saltz, J., Hartman, J., Hainfellner, J., Quesne, J. L., Juco, J. W., Reis-Filho, J., Sanchez, J., Sparano, J., Cucherousset, J., Araya, J. C., Adam, J., Balko, J. M., Saeger, K., Siziopikou, K., Willard-Gallo, K., Weber, K., Pogue-Geile, K. L., Steele, K. E., Emancipator, K., Abduljabbar, K., El Bairi, K., Blenman, K. R. M., Allison, K. H., Korski, K., Pusztai, L., Comerma, L., Buisseret, L., Cooper, L. A. D., Shi, L., Kooreman, L. F. S., Molinero, L., Estrada, M. V., Lacroix-Triki, M., Al Bakir, M., Sebastian, M. M., van de Vijver, M., Balancin, M. L., Dieci, M. V., Mathieu, M. -C., Rebelatto, M. C., Piccart, M., Hanna, M. G., Goetz, M. P., Preusser, M., Khojasteh, M., Sanders, M. E., Regan, M. M., Barnes, M., Christie, M., Misialek, M., Ignatiadis, M., van Bockstal, M., Castillo, M., Amgad, M., Harbeck, N., Tung, N., Laudus, N., Sirtaine, N., Burchardi, N., Ternes, N., Radosevic-Robin, N., Gluz, O., Grimm, O., Nuciforo, P., Jank, P., Gonzalez-Ericsson, P., Kirtani, P., Jelinic, P., Watson, P. H., Savas, P., Francis, P. A., Russell, P. A., Singh, R., Kim, R. S., Pierce, R. H., Hills, R., Leon-Ferre, R., de Wind, R., Shui, R., De Clercq, S., Leung, S., Tabbarah, S., Souza, S. C., O'Toole, S., Swain, S., Dudgeon, S., Willis, S., Ely, S., Kim, S. -R., Bedri, S., Irshad, S., Liu, S. -W., Goel, S., Hendry, S., Bianchi, S., Braganca, S., Paik, S., Wienert, S., Fox, S. B., Luen, S. J., Naber, S., Schnitt, S. J., Sua, L. F., Lakhani, S. R., Fineberg, S., Soler, T., Gevaert, T., D'Alfonso, T., John, T., Sugie, T., Kurkure, U., Bossuyt, V., Manem, V., Camara, V. P., Tong, W., Chen, W., Yang, W., Tran, W. T., Wang, Y., Yuan, Y., Allory, Y., Husain, Z., Bago-Horvath, Z., Division of Pathology and Laboratory Medicine, Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Charité, Institute of Pathology, Translational Tumorpathology Unit, German Breast Group, Breast Cancer Translational Research Laboratory, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), University of the Sunshine Coast (USC), European Institute of Oncology [Milan] (ESMO), Breakthrough Breast Cancer Centre, London Institute of Cancer, Department of Pathology, The Netherlands Cancer Institute, Division of Experimental Therapy, The Netherlands Cancer Institute NKI/AvL, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Hudeček, Jan [0000-0003-1071-5686], van de Vijver, Koen K [0000-0002-2026-9790], Demaria, Sandra [0000-0003-4426-0499], Badve, Sunil S [0000-0001-8861-9980], Symmans, William Fraser [0000-0002-1526-184X], Rimm, David L [0000-0001-5820-4397], Loi, Sherene [0000-0001-6137-9171], Hall, Jacqueline A [0000-0003-0708-1360], Horlings, Hugo M [0000-0003-4782-8828], Apollo - University of Cambridge Repository, van de Vijver, Koen K. [0000-0002-2026-9790], Badve, Sunil S. [0000-0001-8861-9980], Rimm, David L. [0000-0001-5820-4397], Hall, Jacqueline A. [0000-0003-0708-1360], Horlings, Hugo M. [0000-0003-4782-8828], Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, German Breast Group (GBG), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review Article, lcsh:RC254-282, 631/67/1857, Tumour biomarkers, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 692/53, Internal medicine, Medicine and Health Sciences, medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, 692/4028/67/580, Stromal tumor, Biomarkers, Tumour immunology, business.industry, Risk management framework, review-article, Médecine pathologie humaine, 631/67/1347, Immunotherapy, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, Review article, Clinical trial, Cancérologie, 030104 developmental biology, 030220 oncology & carcinogenesis, Biomarker (medicine), business
Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting., info:eu-repo/semantics/published

Published
2020
Full Text
View/download PDF

22. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Author

Kos, Z, Roblin, E, Kim, RS, Michiels, S, Gallas, BD, Chen, W, van de Vijver, KK, Goel, S, Adams, S, Demaria, S, Viale, G, Nielsen, TO, Badve, SS, Symmans, WF, Sotiriou, C, Rimm, DL, Hewitt, S, Denkert, C, Loibl, S, Luen, SJ, Bartlett, JMS, Savas, P, Pruneri, G, Dillon, DA, Cheang, MCU, Tutt, A, Hall, JA, Kok, M, Horlings, HM, Madabhushi, A, van der Laak, J, Ciompi, F, Laenkholm, A-V, Bellolio, E, Gruosso, T, Fox, SB, Araya, JC, Floris, G, Hudecek, J, Voorwerk, L, Beck, AH, Kerner, J, Larsimont, D, Declercq, S, Van den Eynden, G, Pusztai, L, Ehinger, A, Yang, W, AbdulJabbar, K, Yuan, Y, Singh, R, Hiley, C, al Bakir, M, Lazar, AJ, Naber, S, Wienert, S, Castillo, M, Curigliano, G, Dieci, M-V, Andre, F, Swanton, C, Reis-Filho, J, Sparano, J, Balslev, E, Chen, I-C, Stovgaard, EIS, Pogue-Geile, K, Blenman, KRM, Penault-Llorca, F, Schnitt, S, Lakhani, SR, Vincent-Salomon, A, Rojo, F, Braybrooke, JP, Hanna, MG, Soler-Monso, MT, Bethmann, D, Castaneda, CA, Willard-Gallo, K, Sharma, A, Lien, H-C, Fineberg, S, Thagaard, J, Comerma, L, Gonzalez-Ericsson, P, Brogi, E, Loi, S, Saltz, J, Klaushen, F, Cooper, L, Amgad, M, Moore, DA, Salgado, R, Kos, Z, Roblin, E, Kim, RS, Michiels, S, Gallas, BD, Chen, W, van de Vijver, KK, Goel, S, Adams, S, Demaria, S, Viale, G, Nielsen, TO, Badve, SS, Symmans, WF, Sotiriou, C, Rimm, DL, Hewitt, S, Denkert, C, Loibl, S, Luen, SJ, Bartlett, JMS, Savas, P, Pruneri, G, Dillon, DA, Cheang, MCU, Tutt, A, Hall, JA, Kok, M, Horlings, HM, Madabhushi, A, van der Laak, J, Ciompi, F, Laenkholm, A-V, Bellolio, E, Gruosso, T, Fox, SB, Araya, JC, Floris, G, Hudecek, J, Voorwerk, L, Beck, AH, Kerner, J, Larsimont, D, Declercq, S, Van den Eynden, G, Pusztai, L, Ehinger, A, Yang, W, AbdulJabbar, K, Yuan, Y, Singh, R, Hiley, C, al Bakir, M, Lazar, AJ, Naber, S, Wienert, S, Castillo, M, Curigliano, G, Dieci, M-V, Andre, F, Swanton, C, Reis-Filho, J, Sparano, J, Balslev, E, Chen, I-C, Stovgaard, EIS, Pogue-Geile, K, Blenman, KRM, Penault-Llorca, F, Schnitt, S, Lakhani, SR, Vincent-Salomon, A, Rojo, F, Braybrooke, JP, Hanna, MG, Soler-Monso, MT, Bethmann, D, Castaneda, CA, Willard-Gallo, K, Sharma, A, Lien, H-C, Fineberg, S, Thagaard, J, Comerma, L, Gonzalez-Ericsson, P, Brogi, E, Loi, S, Saltz, J, Klaushen, F, Cooper, L, Amgad, M, Moore, DA, and Salgado, R

Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.

Published
2020

23. Synchronous and Metachronous Breast and Ovarian Cancer: Experience From Two Large Cancer Center

Author

Tasca, G, Dieci, M, Baretta, Z, Faggioni, G, Montagna, M, Nicoletto, M, Peccatori, F, Guarneri, V, Colombo, N, Tasca G., Dieci M. V., Baretta Z., Faggioni G., Montagna M., Nicoletto M. O., Peccatori F. A., Guarneri V., Colombo N., Tasca, G, Dieci, M, Baretta, Z, Faggioni, G, Montagna, M, Nicoletto, M, Peccatori, F, Guarneri, V, Colombo, N, Tasca G., Dieci M. V., Baretta Z., Faggioni G., Montagna M., Nicoletto M. O., Peccatori F. A., Guarneri V., and Colombo N.

Abstract

Purpose: We aimed to evaluate the clinico-pathological characteristics and survival outcomes of patients with synchronous or metachronous breast cancer (BC) and ovarian cancer (OC). Materials and Methods: Patients with synchronous or metachronous BC and OC were retrospectively identified at two large cancer centers. Clinico-pathological characteristics, BRCA1/2 status and follow-up data were gathered. Patients were classified according to the first cancer diagnosis in the following groups: Breast Cancer first, Ovarian Cancer first, Synchronous Breast and Ovarian Cancer. Overall survival (OS) was calculated as the time interval between each cancer diagnosis to death or last follow-up. Results: Overall, 270 patients were included: n = 194 (72%) in BC first group, n = 51 (19%) in OC first, and n = 25 (9%) in synchronous. BRCA status was available for 182 (67.4%) patients and 112 (62%) harbored pathogenetic mutations. BC first group included more frequently patients with BRCA mutation, triple negative BC phenotype and more aggressive OC features. Median time between the two diagnosis was longer in BC first group vs OC first group (95 vs 68 months, p = 0.021). A total of 105 OS events occurred, mostly related to OC (70.5%). We observed no differences in terms of OS according to the first cancer diagnosis. Age >50 years and advanced OC stage were negative independent prognostic factors for OS from the first diagnosis. Conclusions: In this cohort of patients with BC and OC, survival was dominated by OC related mortality. These data may be useful to plan and carry out adequate and timely surveillance programs and preventive measures.

Published
2020

24. Targeted next-generation sequencing identifies genomic abnormalities potentially driving the prognosis of early-stage invasive lobular breast carcinoma patients stratified according to a validated clinico-pathological model

Author

Carbognin, L., Simbolo, M., Calio, A., Vicentini, C., Delfino, P., Sperduti, I., Fassan, M., Schettini, F., Dieci, M. V., Griguolo, G., Pilotto, S., Fiorio, E., Arpino, G., Guarneri, V., De Placido, S., Conte, P., Manfrin, E., Brunelli, M., Scambia, Giovanni, Scarpa, A., Tortora, Giampaolo, Bria, Emilio, Scambia G. (ORCID:0000-0003-2758-1063), Tortora G. (ORCID:0000-0002-1378-4962), Bria E. (ORCID:0000-0002-2333-704X), Carbognin, L., Simbolo, M., Calio, A., Vicentini, C., Delfino, P., Sperduti, I., Fassan, M., Schettini, F., Dieci, M. V., Griguolo, G., Pilotto, S., Fiorio, E., Arpino, G., Guarneri, V., De Placido, S., Conte, P., Manfrin, E., Brunelli, M., Scambia, Giovanni, Scarpa, A., Tortora, Giampaolo, Bria, Emilio, Scambia G. (ORCID:0000-0003-2758-1063), Tortora G. (ORCID:0000-0002-1378-4962), and Bria E. (ORCID:0000-0002-2333-704X)

Abstract

Introduction: The clinico-pathological and molecular factors that drive the prognosis of invasive lobular breast carcinoma (ILC) are not entirely explored. In this regard, the development and validation of a prognostic model for ILC and the investigation of the distribution of molecular abnormalities (focusing on CDK4/6 alterations) according to prognosis were the aims of this study. Patients and methods: Two clinico-pathological multi-center data-sets of early-stage ILC patients (Training/Validation Set, TS/VS) were gathered. A 3-class model was developed according to the multivariate analysis for disease-free-survival (DFS) and externally validated. Mutational, copy number variation and transcriptomic analyses by targeted next generation sequencing (NGS) were performed (and validated with quantitative PCR) in an explorative cohort of patients with poor and good prognosis. Results: Data from overall 773 patients (TS/VS: 491/282) were gathered. The developed model significantly discriminated low/intermediate/high risk in the TS (10-years DFS: 76.3%/67.6%/39.8%, respectively, p<0.0001) and in the VS (p<0.0001). In the explorative cohort for molecular analysis (34 patients), CDK4 gain was present exclusively in the poor prognosis group (35.0%, p = 0.03; OR 7.98, 95%CI 1.51–42.1, p = 0.014). Moreover, CDK4 and 6 overexpression showed a trend toward an association with poor prognosis (OR 2.7, 95%CI 0.4–18.1, p = 0.3; OR 3.29, 95%CI 0.56–19.25, p = 0.18). Conclusions: A risk stratification model, able to accurately separate early-stage ILC patients’ prognosis into different risk classes according to clinico-pathological variables, allowed to investigate potential biomarkers of prognosis with targeted NGS. CDK4 gain is suggested for future validation as a prognostic biomarker and a potential therapeutic opportunity in ILC patients.

Published
2020

28. Impact of 21-Gene Breast Cancer Assay on Treatment Decision for Patients with T1–T3, N0–N1, Estrogen Receptor-Positive/Human Epidermal Growth Receptor 2-Negative Breast Cancer: Final Results of the Prospective Multicenter ROXANE Study

Author

Dieci, M. V., Guarneri, V., Zustovich, F., Mion, M., Morandi, P., Bria, Emilio, Merlini, L., Bullian, P., Oliani, C., Gori, S., Giarratano, T., Orvieto, E., Griguolo, G., Michieletto, S., Saibene, T., Del Bianco, P., De Salvo, G. L., Conte, Pietro, Bria E. (ORCID:0000-0002-2333-704X), Dieci, M. V., Guarneri, V., Zustovich, F., Mion, M., Morandi, P., Bria, Emilio, Merlini, L., Bullian, P., Oliani, C., Gori, S., Giarratano, T., Orvieto, E., Griguolo, G., Michieletto, S., Saibene, T., Del Bianco, P., De Salvo, G. L., Conte, Pietro, and Bria E. (ORCID:0000-0002-2333-704X)

Abstract

Background: The ROXANE Italian prospective study evaluated the impact of the 21-gene Recurrence Score (RS) results on adjuvant treatment decision for patients with early breast cancer. Materials and Methods: Nine centers participated. Physicians used the RS test whenever unsure about adjuvant treatment recommendation for patients with estrogen receptor-positive/human epidermal growth receptor 2-negative, T1–T3, N0–N1 early breast cancer. Pre-RS and post-RS treatment recommendations were collected. Results: A total of 251 patients were included. N0 patients (61%) showed higher grade (p <.001) and higher Ki67 (p =.001) and were more frequently progesterone receptor negative (p =.012) as compared with N1 patients. RS results were as follows: <11, n = 63 (25.1%); 11–25, n = 143 (57%); and ≥26, n = 45 (17.9%). Higher RS was found in N0 vs. N1 patients (p =.001) and in cases of G3 (p <.001) and higher Ki67 (p <.001). The rate of change in treatment decision was 30% (n = 75), mostly from chemotherapy (CT) plus hormone therapy (CT + HT) to hormone therapy (HT; 76%, n = 57/75). The proportion of patients recommended to CT + HT was significantly reduced from pre-RS to post-RS (52% to 36%, p <.0001). CT use reduction was more evident for N1 patients (55% to 27%) than for N0 patients (50% to 42%) and was observed only in cases of RS ≤17. Conclusion: Physicians predominantly used the 21-gene assay in N0 patients with a more aggressive biology or in N1 patients showing more indolent biology. In this selected patient population, the use of RS testing led to a 30% rate of change in treatment decision. In the N1 patient subgroup, the use of RS testing contributed to reduce CT use by more than half. Implications for Practice: This study shows that, even in a context in which physicians recommend a high proportion of patients to endocrine treatment alone before knowing the results of the Recurrence Score (RS) assay, the use of the RS test, whenever uncertainty regarding

Published
2019

29. Erratum to: Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials (Breast Cancer Research and Treatment, (2017), 163, 2, (295-302), 10.1007/s10549-017-4191-y)

Author

Dieci, M. V., Frassoldati, A., Generali, D., Bisagni, G., Piacentini, F., Cavanna, L., Cagossi, K., Puglisi, F., Michelotti, A., Berardi, R., Banna, G., Goubar, A., Ficarra, G., Griguolo, G., Conte, Pierfranco, Guarneri, V., Dieci, M. V., Frassoldati, A., Generali, D., Bisagni, G., Piacentini, F., Cavanna, L., Cagossi, K., Puglisi, F., Michelotti, A., Berardi, R., Banna, G., Goubar, A., Ficarra, G., Griguolo, G., Conte, Pierfranco, and Guarneri, V.

Subjects
Cancer Research, Oncology
Abstract

N/A

Published
2017

30. Electrochemotherapy of superficial tumors - Current status:: Basic principles, operating procedures, shared indications, and emerging applications

Author

Campana, L. G., Miklavcic, Damijan, Bertino, G., Marconato, R., Valpione, S., Imarisio, I., Dieci, M. V., Granziera, E., Cemazar, M., Alaibac, M., and Sersa, G.

Subjects
Bleomycin, Breast cancer, Skin Neoplasms, Electrochemotherapy, Skin cancer, Humans, Head and neck cancer, Melanoma, Neoplasm Metastasis, Neoplasm Recurrence, Local, Cell Proliferation
Abstract

Treatment of superficial tumors with electrochemotherapy (ECT) has shown a steep rise over the past decade and indications range from skin cancers to locally advanced or metastatic neoplasms. Based on reversible electroporation, which is a physical method to achieve transient tumor cell membrane permeabilization by means of short electric pulses, ECT increases cellular uptake of bleomycin and cisplatin and their cytotoxicity by 8,000- and 80-fold, respectively. Standard operating procedures were established in 2006 and updated in 2018. Ease of administration, patient tolerability, efficacy across histotypes, and repeatability are peculiar advantages, which make standard ECT (ie, ECT using fixed-geometry electrodes) a reliable option for controlling superficial tumor growth locally and preventing their morbidity. Consolidated indications include superficial metastatic melanoma, breast cancer, head and neck skin tumors, nonmelanoma skin cancers, and Kaposi sarcoma. In well-selected patients with oropharyngeal cancers, ECT ensures appreciable symptom control. Emerging applications include skin metastases from visceral or hematological malignancies, vulvar cancer, and some noncancerous skin lesions (keloids and capillary vascular malformations). Repeatability and integration with other oncologic therapies allow for consolidation of response and sustained tumor control. In this review, we present the basic principles of ECT, recently updated operating procedures, anesthesiological management, and provide a synthesis of the efficacy of standard ECT across histotypes.

Published
2018

31. De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole: results of the PerELISA neoadjuvant study.

Author

Guarneri, V, Dieci, M V, Bisagni, G, Frassoldati, A, Bianchi, G V, Salvo, G L De, Orvieto, E, Urso, L, Pascual, T, Paré, L, Galván, P, Ambroggi, M, Giorgi, C A, Moretti, G, Griguolo, G, Vicini, R, Prat, A, and Conte, P F

Subjects
*HORMONE receptor positive breast cancer, *BREAST cancer, *LETROZOLE, *CANCER patients, *EPIDERMAL growth factor receptors
Published
2019
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32. Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer.

Author

Dieci, M V, Conte, P, Bisagni, G, Brandes, A A, Frassoldati, A, Cavanna, L, Musolino, A, Giotta, F, Rimanti, A, Garrone, O, Bertone, E, Cagossi, K, Sarti, S, Ferro, A, Piacentini, F, Maiorana, A, Orvieto, E, Sanders, M, Miglietta, F, and Balduzzi, S

Subjects
*PROGRESSION-free survival, *HORMONE receptor positive breast cancer, *BREAST cancer, *LYMPHOCYTES, *BREAST cancer patients, *TRASTUZUMAB
Abstract

Background There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. Patients and methods Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan–Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years. Results Median TILs was 5% (Q1–Q3 1%–15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59–0.89, P  =   0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P  =   0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41–0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71–1.12; test for interaction P  =   0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09–2.80, P =0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05–1.09, P  =   0.064), resulting in a significant interaction (P  =   0.015). Conclusions TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy. [ABSTRACT FROM AUTHOR]

Published
2019
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33. Integrated evaluation of PAM50 subtypes and immune modulation of pCR in HER2-positive breast cancer patients treated with chemotherapy and HER2-targeted agents in the CherLOB trial.

Author

Dieci, M. V., Prat, A., Tagliafico, E., Paré, L., Ficarra, G., Bisagni, G., Piacentini, F., Generali, D. G., Conte, P., and Guarneri, V.

Subjects
*IMMUNOREGULATION, *BREAST biopsy, *LYMPHOCYTES, *MEDICAL statistics, BREAST cancer chemotherapy
Abstract

Background: The aim of this work was to evaluate the impact of (and relative contribution of) tumor-related and immunerelated diversity of HER2-positive disease on the response to neoadjuvant chemotherapy plus anti-HER2 agents. Patients and methods: The CherLOB phase II study randomized 121 HER2-positive breast cancer patients to neoadjuvant chemotherapy plus trastuzumab, lapatinib or both. Tumor samples from diagnostic core biopsy were centralized. Tumor-infiltrating lymphocytes (TILs) were evaluated on H&E slides. Intrinsic subtyping was carried out using the researchbased 50-gene prediction analysis of a microarray (PAM50) subtype predictor. Immune-related gene signatures were also evaluated. Results: Continuous Str-TILs and It-TILs were significantly associated with pCR [OR 1.03, 95% CI 1.02-1.05 (P < 0.001) and OR 1.09, 95% CI 1.04-1.15 (P < 0.001) for Str-TILs and It-TILs, respectively]. According to PAM50, the subtype distribution was as follows: HER2-enriched 26.7%, Luminal A 25.6%, Luminal B 16.3%, Basal-like 14% and Normal-like 17.4%. The highest rate of pCR was observed for the HER2-enriched subtype (50%), followed by Basal-like, Luminal B and Luminal A (2 test, P = 0.026). Immune gene signatures significantly associated with pCR in univariate analyses were identified: most of them maintained a significant association with pCR in multivariate analyses corrected for PAM50 subtypes, whereas TILs did not. Conclusions: In this study, both tumor-related and immune-related features contribute to the modulation of pCR after neoadjuvant chemotherapy plus anti-HER2 agents. Immune signatures rather than TILs added significant prediction of pCR beyond PAM50 intrinsic subtypes. [ABSTRACT FROM AUTHOR]

Published
2016
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37. Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy.

Author

Luen, S J, Salgado, R, Dieci, M V, Vingiani, A, Curigliano, G, Gould, R E, Castaneda, C, D'Alfonso, T, Sanchez, J, Cheng, E, Andreopoulou, E, Castillo, M, Adams, S, Demaria, S, Symmans, W F, Michiels, S, and Loi, S

Subjects
*TRIPLE-negative breast cancer, *CANCER chemotherapy, *BREAST cancer patients, *LIKELIHOOD ratio tests, *LYMPHOCYTES
Abstract

Background For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC. Patients and methods We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs. Results A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10–40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ  = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P  =   0.005), nodal stage (P  =   0.032), but did not differ by RCB class (P  =   0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79–0.92; P  <   0.001), and improved OS (HR: 0.87; 95% CI 0.80–0.94; P  <   0.001), and remained significant predictors in multivariate analysis (RFS P  =   0.032; OS P  =   0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P  <   0.001 for RFS; P  =   0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (P Int=0.003) and OS (P Int=0.008) with a greater magnitude of positive effect observed for RCB class II than class III. Conclusions TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II. [ABSTRACT FROM AUTHOR]

Published
2019
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39. Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials

Author

Maria Vittoria Dieci, Aicha Goubar, Giancarlo Bisagni, Gaia Griguolo, Daniele Generali, Valentina Guarneri, A. Michelotti, Antonio Frassoldati, Rossana Berardi, Fabio Puglisi, Guido Ficarra, Katia Cagossi, Federico Piacentini, Giuseppe Luigi Banna, Pierfranco Conte, Luigi Cavanna, Dieci, M. V., Frassoldati, A., Generali, D., Bisagni, G., Piacentini, F., Cavanna, L., Cagossi, K., Puglisi, F., Michelotti, A., Berardi, R., Banna, G., Goubar, A., Ficarra, G., Griguolo, G., Conte, P., and Guarneri, V.

Subjects
0301 basic medicine, Oncology, Cancer Research, Receptor, ErbB-2, medicine.medical_treatment, Tumor-infiltrating lymphocytes, law.invention, ErbB-2, 0302 clinical medicine, Randomized controlled trial, law, Chemotherapy, Endocrine therapy, Ki67, Neoadjuvant, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Breast Neoplasms, Chemotherapy, Adjuvant, Female, Humans, Lymphocytes, Tumor-Infiltrating, Middle Aged, Neoadjuvant Therapy, Nitriles, Prospective Studies, Quinazolines, Receptors, Cell Surface, Treatment Outcome, Triazoles, Receptors, 80 and over, Lymphocytes, Prospective cohort study, Adjuvant, Neoadjuvant therapy, Tumor, 030220 oncology & carcinogenesis, Letrozole, Cell Surface, Cohort, Nitrile, Breast Neoplasm, Human, Receptor, medicine.drug, medicine.medical_specialty, Socio-culturale, Tumor-infiltrating lymphocyte, Lapatinib, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Tumor-Infiltrating, Antineoplastic Combined Chemotherapy Protocol, business.industry, Quinazoline, medicine.disease, Prospective Studie, 030104 developmental biology, Triazole, business, Biomarkers
Abstract

PURPOSE: The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response. METHODS: Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed. RESULTS: StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the low vs high StrTIL group (64% vs 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (-41%) was observed for high StrTIL cases treated with chemotherapy. CONCLUSIONS: This hypothesis-generating study suggests that in HR+/HER2- breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.

Published
2017
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40. Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer

Author

Nadia Naldi, Katia Cagossi, Federico Piacentini, Daniela Boggiani, Antonino Musolino, Daniele Zanoni, Luca Gianni, Daniele Generali, Anita Rimanti, Pierfranco Conte, P. Sgargi, Maria Vittoria Dieci, Valentina Guarneri, Massimo Ambroggi, Samanta Sarti, Giancarlo Bisagni, Andrea Ardizzoni, Musolino, GIUSEPPE ANTONIO, Naldi, N., Dieci, M. V., Zanoni, D., Rimanti, A., Boggiani, D., Sgargi, P., Generali, Daniele, Piacentini, F., Ambroggi, M., Cagossi, K., Gianni, L., Sarti, S., Bisagni, G., Ardizzoni, A., Conte, P. F., Guarneri, V., Musolino, A, Generali, D. G., and Ardizzoni, Andrea

Subjects
0301 basic medicine, Oncology, Time Factors, Pharmacogenomic Variants, Receptor, ErbB-2, Pharmacology, Immunoglobulin G, 0302 clinical medicine, Gene Frequency, Trastuzumab, HER2 Positive Breast Cancer, Antineoplastic Combined Chemotherapy Protocols, Preoperative chemotherapy, skin and connective tissue diseases, Receptor, Mastectomy, Randomized Controlled Trials as Topic, biology, Middle Aged, Neoadjuvant Therapy, Phenotype, Treatment Outcome, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Molecular Medicine, Female, medicine.drug, Adult, medicine.medical_specialty, Genotype, Genetics, Breast Neoplasms, Lapatinib, Polymorphism, Single Nucleotide, Disease-Free Survival, 03 medical and health sciences, Breast cancer, Clinical Trials, Phase II as Topic, Genetic, Internal medicine, mental disorders, medicine, Biomarkers, Tumor, Humans, neoplasms, Protein Kinase Inhibitors, Aged, Retrospective Studies, business.industry, Receptors, IgG, medicine.disease, Molecular medicine, Pharmacogenomic Testing, 030104 developmental biology, Pharmacogenetics, biology.protein, Quinazolines, business
Abstract

Lapatinib enhances antibody-dependent cell-mediated cytotoxicity (ADCC) activity of trastuzumab. FcγR polymorphisms have been associated with both ADCC and clinical activity of trastuzumab in HER2+ breast cancer (BC) patients (pts). We analyzed FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms in the CHER-LOB trial population of HER2+ BCs treated with preoperative chemotherapy plus trastuzumab (arm A), lapatinib (arm B) or both (arm C). Genotyping was successfully performed in 73/121 (60%) pts. A significant improvement in pathological complete response (pCR) rate was observed for the combination arm C, but only in FcγRIIIa V allele carriers (C vs A, 67 vs 27%, P=0.043; C vs B, 67 vs 22%, P=0.012). An independent interaction between arm C and FcγRIIIa V allele was found for pCR (odds ratio=9.4; 95% confidence interval, 2.3-39.6; P=0.003). No significant associations were observed between pCR and FcγRIIa polymorphism, and between pre-treatment tumor-infiltrating lymphocytes and FcγR polymorphisms. Our study provides evidence for a FcγRIIIa V allele-restricted pCR benefit from neoadjuvant trastuzumab plus lapatinib in HER2+ BC.

Published
2016

42. Characteristics and clinical outcomes of breast cancer in young BRCA carriers according to tumor histology.

Author

Agostinetto E, Bruzzone M, Hamy AS, Kim HJ, Chiodi C, Bernstein-Molho R, Linn S, Pogoda K, Carrasco E, Derouane F, Bajpai J, Nader-Marta G, Lopetegui-Lia N, Partridge AH, Cortesi L, Rousset-Jablonski C, Giugliano F, Renaud T, Ferrari A, Paluch-Shimon S, Fruscio R, Cui W, Wong SM, Vernieri C, Ruddy KJ, Dieci MV, Matikas A, Rozenblit M, Aguilar Y Mendez D, De Marchis L, Borea R, Puglisi F, Pistelli M, Kufel-Grabowska J, Di Rocco R, Mariamidze E, Atzori F, Kourie HR, Popovic L, de Azambuja E, Blondeaux E, and Lambertini M

Subjects
Humans, Female, Retrospective Studies, Adult, BRCA1 Protein genetics, Young Adult, Prognosis, Breast Neoplasms genetics, Breast Neoplasms pathology, BRCA2 Protein genetics
Abstract

Background: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer., Methods: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival., Results: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index., Conclusions: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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43. Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers.

Author

Arecco L, Bruzzone M, Bas R, Kim HJ, Di Meglio A, Bernstein-Molho R, Hilbers FS, Pogoda K, Carrasco E, Punie K, Bajpai J, Agostinetto E, Lopetegui-Lia N, Partridge AH, Phillips KA, Toss A, Rousset-Jablonski C, Curigliano G, Renaud T, Ferrari A, Paluch-Shimon S, Fruscio R, Cui W, Wong SM, Vernieri C, Couch FJ, Dieci MV, Matikas A, Rozenblit M, Aguilar-Y Méndez D, De Marchis L, Puglisi F, Fabi A, Graff SL, Witzel I, Rodriguez Hernandez A, Fontana A, Pesce R, Duchnowska R, Pais HL, Sini V, Sokolović E, de Azambuja E, Ceppi M, Blondeaux E, and Lambertini M

Subjects
Humans, Female, Adult, Retrospective Studies, Prognosis, Disease-Free Survival, Young Adult, Germ-Line Mutation, Heterozygote, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Breast Neoplasms genetics, Breast Neoplasms pathology, Breast Neoplasms mortality, Breast Neoplasms metabolism, BRCA1 Protein genetics, BRCA2 Protein genetics, Receptor, ErbB-2 metabolism, Receptor, ErbB-2 genetics, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism
Abstract

Background: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes., Patients and Methods: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]., Results: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype)., Conclusions: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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46. Major advancements in metastatic breast cancer treatment: when expanding options means prolonging survival.

Author

Miglietta F, Bottosso M, Griguolo G, Dieci MV, and Guarneri V

Subjects
Antineoplastic Combined Chemotherapy Protocols therapeutic use, Female, Humans, Progression-Free Survival, Breast Neoplasms drug therapy
Abstract

In the last years we have witnessed tremendous advancements in the treatment landscape of metastatic breast cancer (MBC), leading to a progressive prolongation of progression-free survival and, in some cases, also of overall survival. This led to a substantial increase of advanced disease treatability. In the present review we comprehensively and critically describe the most significant progresses in the therapeutic scenario of MBC according to BC subtype. In particular, we reviewed studies reporting practice-changing data in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive and triple-negative BC, with also a hint to BRCA-related tumors and the emerging HER2-low-positive category., Competing Interests: Disclosure GG reports personal fees from Eli Lilly and Novartis, outside the submitted work. MVD reports personal fees from Eli Lilly, Exact Sciences, Novartis, Pfizer, Seagen, outside the submitted work. VG reports personal fees from Novartis, Roche, Eli Lilly, MSD, outside the submitted work. The remaining authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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47. Survival after neoadjuvant therapy with trastuzumab-lapatinib and chemotherapy in patients with HER2-positive early breast cancer: a meta-analysis of randomized trials.

Author

Guarneri V, Griguolo G, Miglietta F, Conte PF, Dieci MV, and Girardi F

Subjects
Antineoplastic Combined Chemotherapy Protocols adverse effects, Female, Hormones therapeutic use, Humans, Lapatinib pharmacology, Lapatinib therapeutic use, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local etiology, Randomized Controlled Trials as Topic, Receptor, ErbB-2 metabolism, Receptor, ErbB-2 therapeutic use, Trastuzumab pharmacology, Trastuzumab therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Neoadjuvant Therapy methods
Abstract

Background: Studies testing the addition of lapatinib to neoadjuvant trastuzumab + chemotherapy reported an increase in pathologic complete response (pCR), with, nevertheless, discordant results in terms of survival, mainly due to suboptimal power. We here leverage the meta-analytic approach to resolve these inconsistencies., Methods: We conducted a meta-analysis of randomized phase II/III studies testing lapatinib + trastuzumab in combination with neoadjuvant chemotherapy for human epidermal growth factor receptor (HER2)-positive early breast cancer (BC). Recurrence-free survival (RFS) and overall survival (OS) were adopted as survival endpoints. Pooled hazard ratios (HR) were obtained for the effect of lapatinib + trastuzumab versus trastuzumab, pCR versus no-pCR in the whole study populations and pCR versus no-pCR according to hormone receptor status., Results: Four phase II/III randomized trials were included in the meta-analysis (CALGB 40601, Cher-LOB, NSABP-B41, NeoALTTO) for an overall population of 1410 patients receiving neoadjuvant chemotherapy in association with either trastuzumab, lapatinib or their combination. RFS was significantly improved with dual HER2 blockade as compared to trastuzumab [HR 0.62, 95% confidence interval (CI) 0.46-0.85]. Dual blockade also led to significantly improved OS (HR 0.65, 95% CI 0.43-0.98). For all treatments combined, patients achieving pCR had better RFS and OS than those with residual disease (HR 0.45, 95% CI 0.34-0.60, and HR 0.32, 95% CI 0.22-0.48, for RFS and OS, respectively). In patients with hormone receptor-negative tumors, pCR was associated with 65% and 73% relative reduction of risk of relapse and death, respectively. Patients with hormone receptor-positive tumors also experienced improved RFS if they achieved pCR; however, the benefit was smaller than that in hormone receptor-negative disease., Conclusion: Findings from this meta-analysis further validate the role of pCR as a strong predictor of outcome in patients with HER2-positive BC, especially in hormone receptor-negative disease. Moreover, we provide robust evidence that dual blockade with lapatinib + trastuzumab in combination with neoadjuvant chemotherapy prolongs OS, suggesting that the role of lapatinib could be reconsidered in the early setting., Competing Interests: Disclosure VG reports personal fees from Roche, Novartis, Eli Lilly, MSD, GSK and Gilead, all outside the submitted work. GG reports personal fees from Novartis and Eli Lilly all outside the submitted work. MVD reports personal fees from Lilly, Genomic Health, Novartis and Celgene, all outside the submitted work. PFC reports personal fees from Novartis, Eli Lilly, AstraZeneca, Tesaro, BMS and Roche, all outside the submitted work.All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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48. Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

Author

Condorelli M, Bruzzone M, Ceppi M, Ferrari A, Grinshpun A, Hamy AS, de Azambuja E, Carrasco E, Peccatori FA, Di Meglio A, Paluch-Shimon S, Poorvu PD, Venturelli M, Rousset-Jablonski C, Senechal C, Livraghi L, Ponzone R, De Marchis L, Pogoda K, Sonnenblick A, Villarreal-Garza C, Córdoba O, Teixeira L, Clatot F, Punie K, Graffeo R, Dieci MV, Pérez-Fidalgo JA, Duhoux FP, Puglisi F, Ferreira AR, Blondeaux E, Peretz-Yablonski T, Caron O, Saule C, Ameye L, Balmaña J, Partridge AH, Azim HA, Demeestere I, and Lambertini M

Subjects
Adult, BRCA1 Protein genetics, Female, Germ Cells, Humans, Neoplasm Recurrence, Local etiology, Pregnancy, Reproductive Techniques, Assisted adverse effects, Retrospective Studies, Breast Neoplasms genetics
Abstract

Background: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants., Patients and Methods: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy., Results: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group., Conclusion: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing., Competing Interests: Disclosure EdA has acted as a scientific advisory board member and has received honoraria from Roche/Genentech, Novartis, Seattle Genetics, Zodiacs, Libbs, Pierre Fabre, and Lilly; has received travel grants from Roche/GNE and GlaxoSmithKline (GSK)/Novartis; and has received research grants through his institution from Roche/GNE, AstraZeneca, GSK/Novartis, and Servier, outside the submitted work. FAP has acted as consultant for Ipsen, Roche Diagnostic, and Merck outside the submitted work. CRJ has acted as a scientific advisory board member and her institution has received honoraria from Bristol Myers Squibb (BMS), Theramex, and Roche; and her institution has received speaker's fees from Theramex and BMS, outside the submitted work. AS has acted as a consultant for Eli Lilly, Pfizer, Novartis, and Roche; has received speaker's fees from Teva, Roche, Pfizer, and Novartis; has received travel grants from Neopharm, Celgene, and Medison; and has received grant support from Novartis and Roche, outside the submitted work. CVG has acted as a consultant, as a scientific advisory board member, and has received speaker's fees from Roche, Novartis, Pfizer, Lilly, and Merck Sharp & Dohme (MSD); and has received research funding from AstraZeneca, Roche, and Pfizer, outside the submitted work. OCC has acted as a scientific advisory board member for Ascires Sistemas Genómicos; and has received grant support from Roche Diagnostics, Neomedic, and Takeda, outside the submitted work. KP has acted as a scientific advisory board member for AstraZeneca, Eli Lilly, Gilead Sciences, MSD, Novartis, Pierre Fabre, Roche, Teva, and Vifor Pharma; has acted as a consultant for AstraZeneca, Novartis, Pfizer, and Roche; has received speaker's fees from Eli Lilly, Medscape, MSD, Mundi Pharma, Novartis, Pfizer, and Roche; has received travel grants from AstraZeneca, Novartis, Pfizer, PharmaMar, and Roche, outside the submitted work. FP has acted as a scientific advisory board member and has received speaker's fees from Amgen, AstraZeneca, Daichi-Sankyo, Eisai, Eli Lilly, Ipsen, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Seagen, and Takeda; has received travel grants from Celgene, GlaxoSmithKline, and Roche; and has received research funding from AstraZeneca, Eisai, and Roche, outside the submitted work. ARF has received honoraria from Bayer, Daiichi Sankyo, Novartis, and Roche; and has received travel grants from Roche, outside the submitted work. JB has acted as consultant for AstraZeneca and Pfizer outside the submitted work. ID has acted as a scientific advisory board member and received grant from Roche; has received speaker's fees from Novartis; and has received travel grants from Theramex and Ferring, outside the submitted work. ML has acted as a consultant for Roche, Lilly, AstraZeneca, Exact Sciences, and Novartis; and has received honoraria from Sandoz, Roche, Lilly, Pfizer, Novartis, Ipsen, and Takeda, outside the submitted work. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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49. The role of immune microenvironment in small-cell lung cancer: Distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytes.

Author

Bonanno L, Pavan A, Dieci MV, Di Liso E, Schiavon M, Comacchio G, Attili I, Pasello G, Calabrese F, Rea F, Favaretto A, Rugge M, Guarneri V, Fassan M, and Conte PF

Subjects
Aged, Aged, 80 and over, B7-H1 Antigen biosynthesis, Female, Forkhead Transcription Factors biosynthesis, Humans, Kaplan-Meier Estimate, Lung Neoplasms metabolism, Lung Neoplasms therapy, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Prognosis, Retrospective Studies, Small Cell Lung Carcinoma metabolism, Small Cell Lung Carcinoma therapy, B7-H1 Antigen immunology, Forkhead Transcription Factors immunology, Lung Neoplasms immunology, Small Cell Lung Carcinoma immunology, Tumor Microenvironment immunology
Abstract

Introduction: The prognosis of small-cell lung cancer (SCLC) is dismal and new effective therapies are needed. Immunotherapy looks promising, but no molecular predictive markers are currently available, and data on immune microenvironment are very limited., Methods: We retrospectively analysed 104 SCLC cases. Immunohistochemistry evaluation of PD-L1 was performed both on tumour cells (TCs) and on tumour-infiltrating immune cells (TIICs) by using anti-PD-L1 22C3 antibody (DAKO) and categorised by using 1% as cut-off point. Tumour-infiltrating lymphocytes (TILs) were characterised by using anti-CD8 and anti-FOXP3 antibodies. Semi-quantitative score was used and categorised as positive versus negative/low. The relation of molecular markers with prognosis and with clinical variables was evaluated., Results: The analysis included 66 stage I-III patients (48 surgically resected, 18 treated with radical-intent chemoradiotherapy) and 38 metastatic cases. In the overall study population, PD-L1 was expressed on TCs and TIICs in 25% and 40% of cases, respectively. The proportion of PD-L1-positive cases was significantly higher in stage I-III versus metastatic patients (32% versus 13%, p: 0.034 for TCs; 51.5% versus 21% for TIICs, p: 0.002). CD8- and FOXP3-positive TILs were present in 59% and 72% of samples, respectively. The presence of FOXP3-TILs was associated with improved prognosis among non-metastatic patients, with a hazard ratio for survival of 0.32 (95% confidence interval [CI]: 0.16-0.7, p: 0.006) for univariate analysis, and 0.37 (95% CI: 0.17-0.81, p: 0.013) for multivariate analysis., Conclusions: Immune contexture of SCLC may differ according to stage. The presence of FOXP3-positive TILs is a potential prognostic marker for stage I-III SCLCs and warrants further investigation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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50. Chemotherapy for advanced HER2-negative breast cancer: Can one algorithm fit all?

Author

Miglietta F, Dieci MV, Griguolo G, Guarneri V, and Conte PF

Subjects
Biomarkers, Tumor metabolism, Breast Neoplasms metabolism, Female, Humans, Algorithms, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Molecular Targeted Therapy methods, Receptor, ErbB-2 metabolism
Abstract

HER2negative (HER2-) metastatic breast cancer (MBC) represents a challenging scenario for clinicians due to its great biological and clinical heterogeneity. Although management of HER2-MBC currently relies on several options, CT still remains a worthwhile strategy to be exploited. However, to date, there is not an univoque algorithm capable of guiding the choice of the proper CT agent/regimen, sequence and duration. Evidence from randomized clinical trials (RCT) and meta-analyses can actually help guiding the decision making process, however the definition of a standard of care for all HER2-MBC patients may be impractical, also in the light of the identification of new promising molecular and immunotherapeutic agents. The purpose of this work is to review available evidence on the role of CT for HER2-MBC with particular emphasis on the need to outline personalized therapeutic strategies for each patient., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2017
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