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Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding geneBreast cancer is the most common cancer among women worldwide. Breast cancer is not a unique disease, but rather a heterogeneous disease, with different subtypes. Lobular breast cancer is the second most common histologic subtype of breast cancer after ductal breast cancer. Lobular breast cancer has some peculiar characteristics that make it a distinct entity in the context of breast cancer. Nevertheless, few clinical studies so far have focused specifically on this subtype. ROSALINE is a clinical study aimed to test entrectinib, a new drug that showed promising activity in preliminary research studies, in combination with endocrine therapy in women with lobular breast cancer before surgery. Trial Registration Number: NCT04551495 (ClinicalTrials.gov).

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BACKGROUND: Brain metastases (BM) occur in up to 50% of patients (pts) with HER2+ metastatic breast cancer (MBC) and are associated with high morbidity and mortality. While the treatment outcomes of patients (pts) without BM are largely determined by their extra-cranial activity, the outcomes of pts with BM are also influenced by the treatment’s activity in the central nervous system (CNS). TKI-based regimens, have been incorporated into the management of pts with HER2+ MBC. This systematic review aims to assess the clinical outcomes of in pts with or without BM treated with TKI-containing regimens vs those treated with non-TKI-containing regimens. METHODS: A systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings (ASCO, SABCS, ESMO, and ESMO Breast) up to June 20, 2021, was conducted to identify randomized clinical trials (RCT) comparing systemic therapies with anti-HER2 TKI-containing regimens and non-TKI-regimens in pts with HER2+ MBC (PROSPERO ID: CRD42021252332). Studies were screened for the availability of data on progression-free survival (PFS) and overall survival (OS) in subgroups of pts with and without BM at baseline. A random-effect model was used to calculate PFS and OS, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). The Higgins I2 index was used to evaluate the heterogeneity between studies. To assess whether the pooled HRs estimates were stable or strongly dependent on one or few studies, sensitivity analyses were conducted by interactively recalculating the pooled HRs estimates after exclusion of each single study. RESULTS: Of 1,671 identified records, 5 RCT were included involving 2,437 pts (490 with and 1,947 without BM at baseline). Intervention arms included tucatinib, lapatinib, pyrotinib or afatinib in combination with cytotoxic chemotherapy ± trastuzumab; control arms included cytotoxic chemotherapy ± trastuzumab or T-DM1. No trial evaluating neratinib met inclusion criteria. All trials allowed the inclusion of pts with stable and asymptomatic BM, while one (HER2CLIMB) also included pts with progressing/untreated BM. Previous treatment with trastuzumab was reported in 92.8% (n=2,262) of the pts. Regarding PFS, a non-statistically significant trend favoring TKI-containing regimens was observed both in pts with BM (HR 0.67, 95% CI 0.41-1.12, p=0.13) and without BM (HR 0.55, 95% CI 0.24-1.26, p=0.16). Substantial heterogeneity was detected in both subgroups (I2 = 64.4%, p=0.024 and I2 = 95.6%, p 0.001, respectively). Sensitivity analysis, excluding each study one by one, demonstrated a significant PFS benefit favoring TKI-containing regimens in pts with BM after the exclusion from the analysis of afatinib (Lux-Breast1), a non-HER2-specific TKI (HR 0.56, 95% CI 0.35-0.90, p=0.016), with no significant heterogeneity (I2 = 46.9%, p=0.13). Regarding OS, a non-statistically significant trend favoring non-TKI regimens was observed both in pts with BM (HR 1.28, 95% CI 0.48-3.40, p=0.62) and without BM (HR 1.02, 95% CI 0.53-1.98, p=0.94). Substantial heterogeneity was detected in both subgroups (I2 = 86.8%, p=0.001 and I2 = 85.7%, p=0.008, respectively). Sensitivity analysis showed no significant impact on OS after exclusion of each study one by one. No publication bias was detected by Egger’s test. CONCLUSION: Our results suggest a similar magnitude of OS and PFS benefit from anti-HER2 TKI-containing regimens in pts with or without BM. Sensitivity analysis including only trials that evaluated regimens containing tucatinib, lapatinib or pyrotinib demonstrated a significant PFS benefit favoring TKI-containing regimens in pts with BM, emphasizing the relevance of CNS involvement for the interpretation of the results of studies evaluating this class of agents. Citation Format: Guilherme Nader-Marta, Diogo Martins-Branco, Elisa Agostinetto, Marco Bruzzone, Marcello Ceppi, Matteo Lambertini, Nuria Kotecki, Ahmad Awada, Evandro de Azambuja. Efficacy of tyrosine kinase inhibitors (TKI) in the treatment of patients with HER2-positive (HER2+) breast cancer with or without brain metastases: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-03.

Clinicians should address the different health needs of cancer survivors (CS). We investigated concerns about physical/psychosocial symptoms and quality of life (QoL) of CS enrolled in our survivorship program. Our primary aim is to describe the CS population and their quality of life, considering both physical and psychosocial issues, with the intent to identify some possible association with the most frequently observed variables.Adult patients, after ≥ 5 years from achieving complete hematologic or solid tumor remission, were included. The self-administered questionnaire used in the survey was based on the "Cancer Survivors Survey of Needs" (Mayo Clinic).We analyzed data from 191 CS. The median age was 63 years (53 years at diagnosis), and 70% of patients were females. A total of 93 patients (49%) reported a quality of life (QoL) score 2. The most common psychosocial symptom concerns were fear of relapse (53%), genetic counseling (43%), living with uncertainty (35%), defining a new sense of normal (31%), and managing stress (28%). Females are more at risk to develop the following concerns compared with males: pain (40% vs 21%), sleep disturbance (54% vs 30%), weight gain (42% vs 21%), osteoporosis (41% vs 11%), body changes (45% vs 13%), hair or skincare issues (42% vs 16%), hot flashes (40% vs 11%), fear of recurrence (74% vs 54%), and living with a sense of uncertainty (53% vs 29%). Younger patients reported a higher score ( 2) for physical and psychological concerns compared with older patients.In this study, differences in physical and psychological symptoms/stressors among women and younger patients were identified. Female and younger patients appear to report physical and psychosocial concerns more frequently than other subgroups of patients. These observations should be validated and deepened in larger, prospective studies and considered during the long-term follow-up of these subgroups of patients.

Immune checkpoint inhibitor (ICI)-induced cardiotoxicity is a rare immune-related adverse event (irAE) characterized by a high mortality rate. From a pathological point of view, this condition can result from a series of causes, including binding of ICIs to target molecules on nonlymphocytic cells, cross-reaction of T lymphocytes against tumor antigens with off-target tissues, generation of autoantibodies and production of proinflammatory cytokines. The diagnosis of ICI-induced cardiotoxicity can be challenging, and cardiac magnetic resonance (CMR) represents the diagnostic tool of choice in clinically stable patients with suspected myocarditis. CMR is gaining a central role in diagnosis and monitoring of cardiovascular damage in cancer patients, and it is entering international cardiology and oncology guidelines. In this narrative review, we summarized the clinical aspects of ICI-associated myocarditis, highlighting its radiological aspects and proposing a novel algorithm for the use of CMR.

The treatment of breast cancer has improved dramatically over the past century, from a strictly surgical approach to a coordinated one, including local and systemic therapies. Systemic therapies for early-stage disease were initially tested against observation or placebo only in adjuvant trials. Subsequent clinical trials focusing on treatment 'fine-tuning' had a marked increase in cohort size, duration and costs, leading to a growing interest in the neoadjuvant setting in the past decade. Neoadjuvant trial designs have the advantages of enabling the direct evaluation of treatment effects on tumour diameter and offer unique translational research opportunities through the comparative analysis of tumour biology before, during and after treatment. Current technologies enabling the identification of better predictive biomarkers are shaping the new era of (neo)adjuvant trials. An urgent need exists to reinforce collaboration between the pharmaceutical industry and academia to share data and thus establish large databases of biomarker data coupled with patient outcomes that are easily accessible to the scientific community. In this Review, we summarize the evolution of (neo)adjuvant trials from the pre-genomic to the post-genomic era and provide critical insights into how neoadjuvant studies are currently designed, discussing the need for better end points and treatment strategies that are more personalized, including in the post-neoadjuvant setting.

Triple negative breast cancer (TNBC), usually presenting with a very aggressive phenotype, is a heterogeneous entity. We aim to discuss new biomarkers, suitable for prognostic and predictive purposes. We retrospectively collected clinical variables and immunohistochemical characteristics of early TNBCs, specifically focusing on the prognostic and predictive significance of tumor infiltrating lymphocytes (TILs) and androgen receptor (AR) expression, assessing their correlation with clinical variables. Among 159 patients, TILs were significantly higher in younger patients and with lower BMI, and in tumors with higher ki-67 and greater nodal involvement; conversely, AR was significantly higher in older patients and in tumors with lower ki-67. Interestingly and in line with literature, both TILs level and ARs expression were lower within metastatic sites, in patients who developed distant metastases, compared to those found in the primary site. Small (pT1) and node negative tumors were highly represented and no correlation of either TILs or AR with prognosis could be observed. Our findings support the use of stromal TILs to identify a more aggressive, but chemo-sensitive phenotype, mostly represented in younger women, while AR may identify a less aggressive, slow-growing luminal TNBC subtype, more common among older patients. TILs and AR are worth implementing in routine clinical practice to refine prognosis even if, in our case series, we couldn’t identify a significant correlation of the two variables with either disease-free and overall survival.

Triple-negative breast cancer (TNBC) holds a poor prognosis compared to other breast cancer subtypes, and the development of new effective treatment strategies is an unmet medical need. TNBC has traditionally been considered not amenable to treatment with targeted agents due to a lack of actionable targets. Therefore, chemotherapy has remained the mainstay of systemic treatment for many decades. The advent of immunotherapy raised very hopeful expectations in TNBC, possibly due to higher levels of tumor-infiltrating lymphocytes, PD-L1 expression and tumor mutational burden compared to other breast cancer subtypes, that predict an effective anti-tumor immune-engagement. The results of clinical trials testing immunotherapy in TNBC led to the approval of the combination of immune checkpoint inhibitors and chemotherapy in both early and advanced settings. However, some open questions about the use of immunotherapy in TNBC still exist. These include a deeper understanding of the heterogeneity of the disease, identification of reliable predictive biomarkers of response, determination of the most appropriate chemotherapy backbone and appropriate management of potential long-term immune-related adverse events. In this review we aim to examine the available evidence on the use of immunotherapy strategies in both early and advanced TNBC, to critically discuss some of the limitations encountered in clinical research and to summarize data on novel promising immunotherapeutic strategies beyond PD-(L)1 blockade that have been investigated in the most recent trials.

Background: One year of adjuvant trastuzumab with 12 cycles of weekly paclitaxel represents the standard of care for patients with pathological tumor size ≤2cm, node-negative, HER2-positive early breast cancer. Data supporting this indication derive from a single-arm, phase II trial that enrolled 410 patients in the United States only, where the 3 years invasive disease-free survival (DFS) rate was 98.7% (95% CI 97.6-99.8). Therefore, real-world data regarding the clinical outcomes of these patients are needed to confirm the efficacy and safety of this adjuvant anthracycline-free regimen in this population. Methods: We conducted a retrospective, observational, multicentric study to investigate survival outcomes of patients with stage I HER2-positive early breast cancer treated with adjuvant paclitaxel and trastuzumab in seven selected sites in two countries (Belgium and Italy). Eligible patients were men and women with early breast cancer of pathological tumor size between 5 and 20 mm, node-negative (N0 or N1mic), and treated with weekly adjuvant paclitaxel for 12 weeks and trastuzumab (6 mg/kg every 3 weeks administration for 1 year). Patients with a history of previous cancers were not included. The primary endpoint was disease-free survival (DFS) at 3 years from diagnosis. Thus, an optimal follow-up of 3 years from surgery was required. Baseline clinico-pathological characteristics, treatment data, disease recurrences and survival status were extracted from medical records. Survival analysis was performed using log-rank regression test. Results: Overall, 240 patients who received their adjuvant treatment between January 2014 and December 2018 were included in the analysis. The median age was 59.5 years (IQR 50.0-66.9), and 69.6% of patients were post-menopausal at the time of diagnosis. Seventy (31.8%) patients had hypertension and 20 (8.3%) had other cardiac comorbidities. Ductal carcinoma was the most represented histological type (86.3%). The median tumor size was 12mm (IQR 9-15), only seven (2.9%) patients had N1miC, and the majority of tumors (85.0%) were ER-positive. Breast-conserving surgery was performed in 80.8% of patients and 78.2% of patients had adjuvant radiotherapy. The median number of administrated cycles of weekly paclitaxel was 12 (range 1-12) and for trastuzumab 18 (range 1-19). Only one patient stopped trastuzumab prematurely because of safety reason. Aromatase inhibitors were the most frequently administered endocrine therapy (75.7% of patients with ER-positive disease). With a median follow-up of 4.7 (IQR 3.6-5.6) years, we observed a 3-year DFS rate of 98.8% (95% CI 96.2-99.6), with only three disease recurrences (one local and two distant) and four deaths (none of which was breast cancer related) during the duration of the follow-up. Conclusions: In this real-world clinical outcome of patients with stage I HER2-positive breast cancer treated with adjuvant trastuzumab and paclitaxel appeared excellent, with a 1.2% rate of recurrence at 3 years. Our data support the efficacy of an anthracycline-free regimen in this population. A longer follow-up will provide more mature data on overall survival and late relapses, especially in the ER-positive subgroup of patients. Citation Format: Veronique Debien, Elisa Agostinetto, Marianna Sirico, Flavia Jacobs, Chiara Molinelli, Michel Moreau, Marianne Paesmans, Ugo De Giorgi, Armando Santoro, Donatienne Taylor, François P. Duhoux, Andrea Botticelli, Giacomo Barchiesi, Matteo Lambertini, Evandro de Azambuja, Martine Piccart. Real-world clinical outcomes of patients with stage I HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-04.

Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) are the standard first-line treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (HR+/HER2- aBC). HER2-low BC, which is defined by an IHC score for HER2 of 1+ or 2+ with negative ISH assay, accounts for more than half of all HR+/HER2- aBC cases, and it is associated with remarkable clinical benefit from the novel anti-HER2 antibody drug conjugate (ADC) trastuzumab-deruxtecan. Evidence on the prognostic impact of HER2-low status is controversial in both limited-stage and advanced BC. Here, we sought to investigate the possible prognostic relevance of HER2-low status in a population of aBC patients treated with CDK4/6i plus ET. Methods: We conducted a retrospective-prospective study in six Italian Cancer Centers to investigate the impact of HER2 status (low vs. 0) on the progression-free survival (PFS) and overall survival (OS) of consecutive HR+/HER2- aBC patients treated with CDK4/6i plus ET (aromatase inhibitors or fulvestrant) as a first-line therapy. In the main study analysis, we considered HER2 status in the last tumor assessment (i.e., primary tumor, or, when available, a metastatic lesion). We also performed a subgroup analysis including only patients with HER2 status evaluation in a metastatic lesion collected before CDK4/6i plus ET therapy initiation. The association between HER2 status (low vs. 0) and PFS or OS was evaluated using log-rank test and Cox regression modeling. Results: We evaluated 767 consecutive HR+/HER2- aBC patients treated with CDK4/6i plus ET between January 2017 and January 2022. Of these, 436 patients (56.8%) received CDK4/6i plus ET as a first-line therapy, and they were included in this analysis. Median age was 63 years (range 27-87), and 362 patients (83.0%) were postmenopausal. The majority of patients were treated with palbociclib (68.3%), while 91 (20.9%) and 47 (10.8%) patients received ribociclib and abemaciclib, respectively. Regarding HER2 status, 269 (62.9%) patients had HER2-low tumors, while 159 (37.1%) patients had HER2-0 neoplasms. HER2-low status was associated with significantly lower PFS when compared to HER2-0 status [median PFS (mPFS) 23.6 vs. 32.3 months, respectively; p=0.014]. HER2-low status was also associated with significantly worse OS (mOS 48.7 vs 58.3 months, respectively; p=0.025). These results were confirmed in multivariable models adjusting the impact of HER2 status for clinically-relevant covariates, namely estrogen receptor status, Ki-67, age, number of metastatic sites, presence of liver metastases, disease free interval, ECOG Performance Status. In this analysis, HER2-low status, compared with HER2-0 status, was independently associated with worse PFS [adjusted Hazard Ratio (aHR): 1.62; 95% confidence interval (CI): 1.17-2.24; p< 0.01] and OS (aHR: 1.74; 95% CI: 1.09-2.76; p=0.019). Subgroup analysis conducted in the subset of 256 patients with available metastatic tumor samples collected before CDK4/6i plus ET initiation confirmed that HER2-low status (n=157), when compared to HER2-0 status (n=99), was independently associated with worse PFS (mPFS 24.5 vs 35.2 months, p=0.01; aHR 2.07; 95% CI: 1.28-3.34, p< 0.01) and worse OS (mPFS 48.7 vs 72.3 months, p=0.027; aHR 3.12; 95% CI 1.44-6.77, p< 0.01). Conclusions: This multicenter Italian study revealed that HER2-low status has independent, negative prognostic value in patients with HR+/HER2- aBC treated with CDK4/6i plus ET in the first-line setting. Our results suggest that HER2-low status might be associated with different clinical benefit from standard anticancer therapies in specific clinical settings. The definition of treatment algorithms also taking into account HER2 status is a clinical priority in patients with HR+/HER2- aBC. Citation Format: Emma Zattarin, Caterina Sposetti, Rita Leporati, Luigi Mariani, Alice Menichetti, Chiara Corti, Chiara Benvenuti, Giovanni Fucà, Riccardo Lobefaro, Francesca Ligorio, Daniele Presti, Leonardo Provenzano, Andrea Vingiani, Gaia Griguolo, Marianna Sirico, Ottavia Bernocchi, Antonio Marra, Paola Zagami, Elisa Agostinetto, Flavia Jacobs, Pierluigi Di Mauro, Andrea Esposito, Carlo Alberto Giorgi, Luca Lalli, Laura Boldrini, Pier Paolo Maria Berton Giachetti, Ambra Carnevale Schianca, Valentina Guarneri, Rebecca Pedersini, Agnese Losurdo, Alberto Zambelli, Daniele Giulio Generali, Giuseppe Curigliano, Giancarlo Pruneri, Filippo de Braud, Maria Vittoria Dieci, Claudio Vernieri. HER2-02 HER2-Low Status is Associated with Worse Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer Patients Treated With First-Line Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-02.

Breast cancer is the most common malignancy among women worldwide, and HER2-positive breast cancer accounts for approximately 15% of all breast cancer diagnoses. The advent of HER2-targeting therapies has dramatically improved the survival of these patients, significantly reducing their risk of recurrence and death. However, as a significant proportion of patients ultimately develop resistance to these therapies, it is extremely important to identify new treatments to further improve their clinical outcomes. Immunotherapy has revolutionized the treatment and history of several cancer types, and it has already been approved as a standard of care for patients with triple-negative breast cancer. Based on a strong preclinical rationale, immunotherapy in HER2-positive breast cancer represents an intriguing field that is currently under clinical investigation. There is a close interplay between HER2-targeting therapies (both approved and under investigation) and the immune system, and several new immunotherapeutic strategies, including immune checkpoint inhibitors, CAR-T cells and therapeutic vaccines, are being studied in this disease. In this narrative review, we discuss the clinical evidence and the future perspectives of immunotherapy for patients with HER2-positive breast cancer.

Triple negative breast cancer (TNBC) is an area of high unmet medical need in terms of new effective treatment strategies. Although breast cancer is traditionally considered a 'cold' tumor type, TNBC is the most appropriate subtype for immunotherapeutic strategies; this is due to the high level of tumor infiltrating lymphocytes, PD-L1 expression, and tumor mutational burden compared to other breast cancer subtypes.This review examines the available evidence on the use of immunotherapeutic strategies in early and advanced TNBC, discusses the pitfalls and limitations often encountered in clinical research, and summarizes data on novel promising immunomodulatory approaches that have been explored in early-phase trials.PD-1-blockade is approved for stage II/III TNBC and for first-line treatment of PD-L1-positive TNBC patients with metastatic disease and should be considered standard of care. However, question marks and difficulties remain; these include the identification of predictive biomarkers to select patients who benefit from the addition of PD1-blockade and the balance between efficacy and long-term toxicity for an individual patient. Numerous treatment combinations and new immunotherapeutic strategies beyond PD1 blockade are being evaluated, thus reflecting a promising evolution towards a more personalized approach, and extended clinical benefit in TNBC.

Introduction Triple-negative breast cancer (TNBC) is considered the most aggressive breast cancer subtype with the least favorable outcomes. However, recent research efforts have generated an enhanced knowledge of the biology of the disease and have provided a new, more comprehensive understanding of the multifaceted ecosystem that underpins TNBC. Areas covered In this review, the authors illustrate the principal biological characteristics of TNBC, the molecular driver alterations, targetable genes, and the biomarkers of immune engagement that have been identified across the subgroups of TNBC. Accordingly, the authors summarize the landscape of the innovative and investigative biomarker-driven therapeutic options in TNBC that emerge from the unique biological basis of the disease. Expert opinion The therapeutic setting of TNBC is rapidly evolving. An enriched understanding of the tumor spatial and temporal heterogeneity and the surrounding microenvironment of this complex disease can effectively support the development of novel and tailored opportunities of treatment.

Background: Breast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive, and triple negative). Each subtype has distinct clinical-pathological and molecular characteristics and requires tailored treatments. Recent research efforts have been focusing on a new classification, identifying the so-called “HER2-low” category, including tumors characterized by a low level of HER2 expression (immunohistochemistry score 1+ or 2+ without in situ hybridization amplification). Emerging evidence shows that patients with HER2-low tumors can derive benefit from selected anti-HER2 therapies. This represents a major advancement in the field of breast oncology, where a broader proportion of patients with breast cancer can ultimately benefit from new effective targeted treatment strategies. Summary: The antibody-drug conjugate trastuzumab deruxtecan has proven impressive efficacy in patients with HER2-low breast cancer, and several other drugs are currently under investigation in this subset of patients. Additional investigation is needed to address open issues that exist in this field, including appropriate pathological assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs. Key Message: Our review aims to summarize the available evidence regarding HER2-low breast cancer, illustrating the current challenges that are being addressed and the future perspectives in this exciting new field.

In clinical trials testing abemaciclib in patients with hormone-receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer, diarrhea is a very common adverse event (occurring in approximately 85% of patients, any grade). Nonetheless, this toxicity leads to abemaciclib discontinuation in a small proportion of patients (approximately 2%) thanks to the use of effective loperamide-based supportive therapy. We aimed to determine whether the incidence of abemaciclib-induced diarrhea in real-world trials was higher than the one reported in clinical trials, where patients are highly selected, and to evaluate the success rate of standard supportive care in this setting. We conducted a retrospective, observational, monocentric study including 39 consecutive patients with HR+/HER2- advanced breast cancer treated with abemaciclib and endocrine therapy at our institution from July 2019 to May 2021. Overall, diarrhea of any grade occurred in 36 patients (92%), of whom 6 (17%) had diarrhea of grade ≥3. In 30 patients (77%), diarrhea was associated with other adverse events, including fatigue (33%), neutropenia (33%), emesis (28%), abdominal pain (20%), and hepatotoxicity (13%). Loperamide-based supportive therapy was administered to 26 patients (72%). Abemaciclib dose was reduced in 12 patients (31%) due to diarrhea, and treatment was permanently discontinued in 4 patients (10%). In 58% of patients (15/26), diarrhea was effectively managed with supportive care and did not require abemaciclib dose reduction and/or discontinuation. In our real-world analysis, we observed a higher incidence of diarrhea related to abemaciclib compared to data from clinical trials, and a higher rate of permanent treatment discontinuation due to gastrointestinal toxicity. Better implementation of guideline-based supportive care could help to manage this toxicity.

We aimed to determine the distribution of intrinsic subtypes within HER2-low breast cancer (BC), and to describe the prognostic impact of HER2-low status on survival outcomes., info:eu-repo/semantics/published

Background: The role of tumour infiltrating lymphocytes (TILs) as a biomarker in non-invasive breast cancer is unclear. This meta-analysis assessed the prognostic impact of TIL levels in patients with non-invasive breast cancer. Methods: Systematic literature search was performed to identify studies assessing local recurrence in patients with non-invasive breast cancer according to TIL levels (high vs. low). Subgroup analyses per local recurrence (invasive and non-invasive) were performed. Secondary objectives were the association between TIL levels and non-invasive breast cancer subtypes, age, grade and necrosis. Odds ratios (ORs) and 95% confidence intervals (CI) were extracted from each study and a pooled analysis was conducted with random-effect model. Results: Seven studies (N = 3437) were included in the present meta-analysis. High-TILs were associated with a higher likelihood of local recurrence (invasive or non-invasive, N = 2941; OR 2.05; 95%CI, 1.03–4.08; p = 0.042), although with a lower likelihood of invasive local recurrence (N = 1722; OR 0.69; 95%CI, 0.49–0.99; p = 0.042). High-TIL levels were associated with triple-negative (OR 3.84; 95%CI, 2.23–6.61; p < 0.001) and HER2-positive (OR 6.27; 95%CI, 4.93–7.97; p < 0.001) subtypes, high grade (OR 5.15; 95%CI, 3.69–7.19; p < 0.001) and necrosis (OR 3.09; 95%CI, 2.33–4.10; p < 0.001). Conclusions: High-TIL levels were associated with more aggressive tumours, a higher likelihood of local recurrence (invasive or non-invasive) but a lower likelihood of invasive local recurrence in patients with non-invasive breast cancer., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: Preclinical and retrospective studies suggest that beta-blockers are active against breast cancer. We carried out a systematic review and meta-analysis to assess the impact of beta-blockers on the outcomes of patients with early-stage breast cancer. METHODS: A systematic literature search was performed to identify studies comparing outcomes of patients with early-stage breast cancer according to beta-blocker use (yes versus no). The primary endpoint was recurrence-free survival (RFS), defined as the occurrence of breast cancer recurrence or death. Secondary objectives were pathologic complete response (pCR), breast cancer recurrence, breast cancer-specific mortality and overall survival (OS). Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were extracted from each study and a pooled analysis with the random-effect model was conducted. The Higgins' I-squared test was used to quantify heterogeneity. Egger's test was applied to assess publication bias. All P values were two-sided and considered significant if ≤0.05. RESULTS: Overall, 13 studies were included as follows: RFS (6), pCR (2), breast cancer recurrence (6), breast cancer-specific mortality (7) and OS (5). The use of beta-blockers was associated with a significant RFS improvement in the overall population (N = 21 570; HR 0.73; 95% CI, 0.56-0.96; P = 0.025) and in patients with triple-negative disease (N = 1212; HR 0.53; 95% CI, 0.35-0.81; P = 0.003). No significant differences in terms of pCR (N = 1554; OR 0.77; 95% CI, 0.44-1.36; P = 0.371), breast cancer recurrence (N = 37 957; OR 0.66; 95% CI, 0.42-1.03; P = 0.065), breast cancer-specific mortality (N = 64 830; HR 0.77; 95% CI, 0.56-1.08; P = 0.130) or OS (N = 103 065; HR 1.03; 95% CI, 0.87-1.23; P = 0.692) were observed according to beta-blocker use. DISCUSSION: In this meta-analysis, beta-blocker use was associated with a longer RFS in patients with early-stage breast cancer, with a more pronounced effect observed in those with triple-negative disease. Beta-blockers arise as an interesting option to be explored in prospective studies for patients with early-stage breast cancer., SCOPUS: re.j, info:eu-repo/semantics/published

Triple negative breast cancer (TNBC) accounts for approximately 10–15% of all breast cancers and it is associated with a poor prognosis. However, recent new effective treatment strategies have improved its outcomes. The aim of this review is to provide an overview on the emerging therapeutics for TNBC, describing both previously approved therapies that are currently being repurposed, as well as new target therapies that may improve patient outcomes. Emerging therapies are forthcoming in TNBC’s treatment landscape, including new post-neoadjuvant chemotherapy strategies, PARP inhibitors, immune checkpoint inhibitors, and antibody-drug conjugates. Combination of different therapies such as AKT/PI3K/mTOR-inhibitors, other immunotherapeutic agents, CDK-inhibitors, antiandrogens, antiangiogenics, and histone deacetylase inhibitors is under clinical investigation. The treatment landscape for TNBC is gradually evolving towards a more personalized approach with promising expectations.

Since human epidermal growth factor receptor-2 (HER2) characterization, going through clinical research and regulatory approval of HER2-targeted therapies, much has elapsed and is still unfolding. Hitherto, only breast cancer (BC) patients with HER2 immunohistochemistry 3+ or with HER2 gene fluorescence in-situ hybridization (FISH) amplification (a.k.a. HER2-positive BC) have benefited from anti-HER2 agents. In recent years, however, much of the research effort has been expanded, with positive outcomes being reached for formerly known HER2-negative BC that yet express HER2 to some degree (HER2 immunohistochemistry 1+ or 2+, but FISH negative) and are currently being classified as HER2-low BC for the purpose of trial enrollment. In this sense, our aim is to review the body of evidence of HER2-low BC that led to the study of first-generation anti-HER2 agents, like trastuzumab, and how they have failed to achieve any clinical applicability in this setting. In addition, we review new data that is leading to the growing success of the new generation of drugs, especially the promising HER2-directed antibody–drug conjugates. A narrative review is also performed regarding the rationale behind the consolidated and ongoing clinical trials studying anti-HER2 agents in combination with unrelated agents, such as immunotherapy, endocrine therapy, and CDK4/6 inhibitors. Hopefully, all this ongoing research effort will be able to extend the survival benefits seen with anti-HER2 agents in HER2-positive disease, at least to some degree, to the greater proportion of patients with HER2-low BC., SCOPUS: re.j, info:eu-repo/semantics/published

BACKGROUND: The combination of cyclin-dependent kinases 4/6 inhibitors (CDK4/6is) and endocrine therapy (ET) is standard of care for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (BC). However, studies evaluating adjuvant CDK4/6is provided contradictory results thus far. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis to assess if the addition of CDK4/6is to adjuvant ET impacts on survival's outcomes and safety of patients with HR+/HER2- early BC (EBC). This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and was registered in the PROSPERO database (ID: CRD42020218597). A systematic review of PubMed, Cochrane and EMBASE databases and major conference proceedings was performed up to 15 December 2020. All randomized controlled trials including patients with HR+/HER2- EBC treated with CDK4/6is plus ET versus ET alone in the adjuvant setting were included. Pooled hazard ratios (HRs) and odds ratios (ORs) for survival and safety outcomes, respectively, were calculated with 95% confidence intervals (95% CIs) using random effect models. RESULTS: With data available from three studies (N = 12 647), the addition of CDK4/6is to adjuvant ET showed a trend for a benefit in terms of invasive disease-free survival (IDFS; HR 0.85, 95% CI 0.71-1.01; P = 0.071). No significant improvement in distant relapse-free survival was observed (HR 0.83, 95% CI 0.58-1.19; P = 0.311). The risk of all-grade toxicities and early treatment discontinuation increased significantly with the addition of CDK4/6is to ET (OR 9.36, 95% CI 3.46-25.33, P < 0.001, and OR 22.11, 95% CI 9.45-51.69, P < 0.001, respectively). CONCLUSION: The administration of adjuvant CDK4/6is to patients with HR+/HER2- EBC showed a trend for an IDFS benefit and an increase in the risk of toxicities and treatment discontinuation. The role of adjuvant CDK4/6is remains controversial and a longer follow-up of these randomized controlled trials is needed before supporting a straightforward change in clinical practice., SCOPUS: re.j, info:eu-repo/semantics/published

Background Immune checkpoint inhibitors (ICIs) may cause potentially life-threatening adverse events (AEs), but the risk of cardiotoxicity has not been fully investigated. It is also unknown whether ICI combinations increase cardiotoxicity compared with single ICI. We aimed to assess the cardiotoxicity of ICI in a range of tumour types. Methods This systematic review and meta-analysis was conducted according to PRISMA guidelines (PROSPERO registration number: CRD42020183524). A systematic search of PubMed, MEDLINE, Embase databases, and conference proceedings was performed up to 30 June 2020. All randomised clinical trials comparing ICI with other treatments (primary objective) or dual-agent ICI versus single-agent ICI (secondary objective) in any solid tumour were included. Pooled risk ratios (RRs) with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated using random effect models. Results Eighty studies including 35,337 patients were included in the analysis (66 studies with 34,664 patients for the primary endpoint and 14 studies with 673 patients for the secondary endpoint). No significant differences in terms of cardiac AEs were observed between ICI and non-ICI groups (RR 1.14, 95% CI 0.88–1.48, p = 0.326) nor between dual ICI and single ICI groups (RR 1.91, 95% CI 0.52–7.01, p = 0.329). Myocarditis incidence did not significantly differ between ICI and non-ICI groups (RR 1.11, 95% CI 0.64–1.92, p = 0.701) nor between dual ICI and single ICI groups (RR 1.10, 95% CI 0.31–3.87, p = 0.881). No differences were observed in subgroup analyses according to tumour type, setting of disease, treatment line, and type of treatment. Conclusion The use of ICI as single or combination regimens is not associated with increased risk of cardiotoxicity.

Purpose: The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor—positive (HR+), HER2-negative (HER2−), advanced breast cancer (HR+/HER2− aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus. Experimental Design: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR+/HER2− aBC treated with everolimus-exemestane. Results: We evaluated 809 patients with HR+/HER2− aBC treated with everolimus-exemestane as any line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared with patients who are already hyperglycemic at baseline and experience diabetes during everolimus-exemestane therapy (median PFS, 6.34 vs. 10.32 months; HR, 1.76; 95% confidence interval, 1.15–2.69; P = 0.008). Conclusions: The impact of on-treatment glycemia on the efficacy of everolimus-exemestane therapy in patients with HR+/HER2− aBC depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in patients with HR+/HER2− aBC.

Background HER2-positive (HER2+) breast cancer represents a heterogeneous breast cancer subtype, including both estrogen receptor (ER) positive and negative tumours. A deeper understanding of the crosstalk between ER and HER2 receptor pathways has led to the development of treatment strategies consisting of a simultaneous blockade of both signaling pathways, as a reasonable approach to prevent the onset of mechanisms of resistance. Methods This review was based on the material searched on PubMed, MEDLINE and Embase databases and on conference proceedings from major oncology conferences up to December 15, 2020. The search strategy included the following keywords: 'HER2-positive breast cancer', 'CDK 4-6 inhibitors' and 'PI3K inhibitors', and was adapted for use with different bibliographic databases. Results CDK4/6 and PI3K inhibitors are two classes of agents already approved in patients with hormone receptor positive, HER2-negative breast cancer. Recently, promising data with their use have been also shown in HER2+ disease. Results from preclinical and clinical studies are shedding light on the role of these classes of agents in HER2+ breast cancer, and are paving the road for a forthcoming change in clinical practice. Conclusions Treatment landscape for HER2+ breast cancer is rapidly changing, and CDK4/6 and PI3K inhibitors represent a new promising strategy to improve patients' outcomes.

Drug-induced liver injury (DILI) is a challenging clinical event in medicine, particularly because of its ability to present with a variety of phenotypes including that of autoimmune hepatitis or other immune mediated liver injuries. Limited diagnostic and therapeutic tools are available, mostly because its pathogenesis has remained poorly understood for decades. The recent scientific and technological advancements in genomics and immunology are paving the way for a better understanding of the molecular aspects of DILI. This review provides an updated overview of the genetic predisposition and immunological mechanisms behind the pathogenesis of DILI and presents the state-of-the-art experimental models to study DILI at the pre-clinical level.

Cyclin-dependent kinase 4–6 inhibitors (CDK4-6i) represent a major advance in the treatment of patients with HR-positive (HR+), HER2-negative (HER2−) metastatic breast cancer (mBC), having become the standard of care in first-line, and a valid treatment option in second-line in combination with endocrine therapy (ET).1 These trials have consistently showed an improvement in progression-free survival and, some of them, in overall survival. Although adjuvant ET significantly reduces the risk of recurrence and death among patients with HR+ early breast cancer (EBC), up to 20% of these patients will experience recurrences in the first 10 years, either with locoregional disease or with distant metastases, which is incurable in the latter scenario.2 Therefore, it is of paramount importance to define new treatment strategies to minimise this recurrence risk and to improve patient outcomes. Therefore, several studies are evaluating the efficacy of CDK4-6i with ET for patients with HR+/HER2− EBC. At the annual meeting of the European Society of Medical Oncology 2020, two of these ongoing studies were presented with controversial results: the MonarchE and the PALbociclib CoLlaborative Adjuvant Study (PALLAS) studies (table 1). The open-label, phase III MonarchE study, included patients with HR+/HER− EBC at ‘high risk’ of relapse defined by ≥4 positive nodes, or 1–3 positive nodes with either tumours ≥5 cm, histological grade 3, or centrally assessed Ki-67 ≥20%.3 Patients were randomised to receive standard ET with or without abemaciclib, at a dosage of 150 mg administered twice daily for 2 years. Primary endpoint was invasive disease-free survival (IDFS). Overall, among the intention-to-treat population of 5637 patients, 323 events were observed. After a median follow-up of 15.5 months, the combination of abemaciclib and ET was associated with a significant IDFS improvement (2-year IDFS rates 92.2% vs 88.7%, HR 0.75, 95% CI 0.60 to 0.93, p=0.01) and distant relapse-free survival (DRFS) (2-year …

The growing availability of more effective therapies has contributed to an increased survival of patients with breast cancer. In hormone receptor-positive early disease, increased survival is strongly correlated with the use of adjuvant endocrine therapy, but this therapy can cause side-effects that have major consequences in terms of treatment adherence and patients' quality of life. In premenopausal breast cancer survivors, these side-effects might be even more prominent due to the abrupt suppression of oestrogen associated with the most intense endocrine therapies. An important ambition of cancer care in the 21st century is to recover pre-cancer quality of life and emotional and social functions, which is only possible through the mitigation of the side-effects of anticancer treatments. This Review presents a comprehensive summary of the efficacy and safety data of the available interventions (hormonal and non-hormonal pharmacological strategies, non-pharmacological approaches, and complementary and alternative medicine) to control selected side-effects associated with adjuvant endocrine therapy (hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, and fatigue), providing updated, evidence-based approaches for their management.

Background:The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials.Patients and methods:This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B).Results:In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively.Conclusions:Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

Indication for neoadjuvant chemotherapy (NACT) in HR+/HER2-negative tumors is controversial. Pathological complete response (pCR) rates range from 0 to 18 % while breast-conserving surgery (BCS) is achievable in up to 60 % of tumors. No pathological feature definitely predicts pCR; lobular and molecular luminal A tumors are less likely to achieve pCR although experiencing better outcomes. Luminal B subtype, high proliferation, lack of progesterone receptor, high tumor-infiltrating lymphocytes are positively associated with increased pCR rates but worse outcomes and the prognostic role of pCR is inconsistent across studies. Molecular intrinsic subtyping and genomic signatures appear as more accurate predictors of benefit from NACT, but larger studies are needed. Anthracycline and taxane-based chemotherapy remains the standard NACT; however, CDK 4/6 inhibitors and immune checkpoint inhibitors are under evaluation. In conclusion, NACT may be proposed for luminal tumors requiring downsizing for BCS after multidisciplinary evaluation, provided that other contraindications to BCS are excluded.

Background: Approximately 30% of patients with early breast cancer present disease relapse after surgery, and technologies that enable the detection of circulating tumor DNA (ctDNA) were shown to identify them earlier than standard imaging. In the present study, we aimed to interrogate the value of the SignateraTM personalized ctDNA assay for early detection of disease relapse. Methods: The study included 52 early breast cancer patients undergoing neoadjuvant chemotherapy from an ongoing translational, single-center study at Jules Bordet Institute, Brussels, Belgium. From each patient, primary tumor tissue sections, blood sample for normal DNA, and serial plasma samples were sent to NATERA Inc for ctDNA detection using the SignateraTM assay. Plasma samples were collected before the initiation of neoadjuvant chemotherapy (baseline), after neoadjuvant chemotherapy, before surgery (pre-surgery), and at follow-up post-surgery. Whole exome sequencing (WES) was performed on the primary tumor tissue and matched normal DNA to design a patient-specific ctDNA assay. The unique set of SNV’s identified in WES were tracked in serial plasma samples. Associations between baseline ctDNA detection and standard clinicopathological characteristics and primary tumor point mutations or copy number aberrations were evaluated. Association between ctDNA detection, pathological complete response (pCR) and event-free survival (EFS) were explored. Fisher, Mann-Whitney and Kruskal-Wallis tests were used to compare variables. Log-rank tests and Cox regressions were used for survival analyses. Hazard ratios (HRs) and confidence intervals (CIs) were obtained from Cox regressions. For multivariable tests, logistic regressions were used for binary outcomes and Cox regressions for survival outcomes. P-values were obtained by comparing models with and without the variable of interest using Chi-square test in ANOVAs. Results: Forty-four out of 52 (85%) initially selected patients had the required tumor cellularity (≥ 20%) and adequate tumor DNA quantity and quality and had personalized ctDNA assays designed. In these 44 patients, 154 plasma samples were successfully processed including 38, 41, 75, 38 at baseline, pre-surgery, follow-up (any timepoint) and last follow-up timepoint, respectively. Twenty (45%) patients had hormone receptor positive/HER2-negative, 13 (30%) triple-negative and 11 (25%) HER2-positive breast cancers. Detection of ctDNA was observed in 22 of 38 (58%) patients at baseline and was significantly associated with Ki67>20% and MYC copy number gain in the primary tumor. ctDNA detection at pre-surgery and at last follow-up was observed in 2 of 41 (5%) and 2 of 38 (5%) patients respectively. All patients who achieved pCR were ctDNA-negative at the pre-surgical time point. With a median follow-up of 3.03 years (range 0.39 - 5.85), we observed 8 relapses (7 distant and 1 local, respectively). After adjusting for pCR, ctDNA detection was associated with shorter EFS at pre-surgery and at last follow-up time points (HR: 53, 95% CI: 4.5-624, p Citation Format: Elisa Agostinetto, Frédéric Cailleux, Matteo Lambertini, Françoise Rothé, Hsin-Ta Wu, Mustafa Balcioglu, Himanshu Sethi, Delphine Vincent, Giulia Viglietti, Andrea Gombos, Andreas Papagiannis, Isabelle Veys, Ahmad Awada, Christos Sotiriou, Ekaterina Kalashnikova, Alexey Aleshin, Denis Larsimont, David Venet, Michail Ignatiadis. Detection of circulating tumor DNA post neoadjuvant chemotherapy using a personalized assay is associated with disease relapse [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-01-06.

Aim: Trastuzumab prolongs progression-free and overall survival in HER2+ breast cancer (BC), but these are associated with increased distant recurrences and central nervous system metastases (CNSm). We retrospectively evaluated outcome and prognostic factors in CNSm and non-CNSm patients. Methods: Records of HER2+ BC treated in 2000–2017 were reviewed. Results: 283/1171 (24%) HER2+ BC patients developed metastatic disease. 109/283 patients (39%) have CNSm associated with worse prognosis and increased risk of death (hazard ratio: 4.7; 95% CI: 3.5–6.4). Prognostic factors were: number of CNSm (single vs multiple lesions; 3-year overall survival 39 vs 18%; p = 0.003); brain radiation (30 vs 14%; p < 0.001); new HER2-targeting therapies (30.6 vs 22.5%; p = 0.025). Conclusion: Prognosis of BC patients with CNSm has improved using HER2-targeting therapies but remains poor.

Because the risk of relapse of node-negative breast cancer (BC) is varying, we evaluated the prognosis of patients with this disease and the factors associated with increased risk of relapse.The clinical charts of patients with BC with evidence of negative nodes and with a potential ≥ 5-year follow-up were retrospectively reviewed.We analyzed 1276 patients. Over a median follow-up of 71.6 months (range, 1-227.2 months), we observed 159 events of relapse or death. The median RFS was 170 months. The median overall survival (OS) was 192 months. At univariate analysis, older age, negative hormonal receptors, larger tumor size and higher proliferation index (Ki67) were associated with worse recurrence-free survival (RFS) and OS (P .05); higher grading was associated with worse RFS (P = .01). At multivariate analysis for RFS, age, Ki67 and tumor size confirmed their independent prognostic role. At multivariate analysis for OS, age and positive hormonal receptors showed an independent prognostic role. We observed no differences in prognosis between human epidermal growth factor receptor 2 (HER2) positive and triple-negative (TN) BC, but TNBC showed a worse OS compared with luminal-like BC.In node-negative BC, age, hormone receptor status, tumor size and Ki67 were prognostic factors. The TNBC subtype was not associated with poorer prognosis compared with the HER2-positive subtype, but showed a worse OS compared with luminal-like BC.