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In many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear. Nonetheless, recent data challenge this practice. Here, we discuss the value of routine HER2 assessment for DCIS. HER2-positivity correlates strongly with DCIS grade: around four in five HER2-positive DCIS show high grade atypia. As morphological DCIS grading is prone to interobserver variability, HER2 immunohistochemistry could render grading more robust. Several studies showed an association between HER2-positive DCIS and ipsilateral recurrence risk, albeit currently unclear whether this is for overall, in situ or invasive recurrence. HER2-positive DCIS tends to be larger, with a higher risk of involved surgical margins. HER2-positive DCIS patients benefit more from adjuvant radiotherapy: it substantially decreases the local recurrence risk after lumpectomy, without impact on overall survival. HER2-positivity in pure biopsy-diagnosed DCIS is associated with increased upstaging to invasive carcinoma after surgery. HER2 immunohistochemistry on preoperative biopsies might therefore provide useful information to surgeons, favoring wider excisions. The time seems right to consider DCIS subtype-dependent treatment, comprising appropriate local treatment for HER2-positive DCIS patients and de-escalation for hormone receptor-positive, HER2-negative DCIS patients. [ABSTRACT FROM AUTHOR]

Abstract In many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear. Nonetheless, recent data challenge this practice. Here, we discuss the value of routine HER2 assessment for DCIS. HER2-positivity correlates strongly with DCIS grade: around four in five HER2-positive DCIS show high grade atypia. As morphological DCIS grading is prone to interobserver variability, HER2 immunohistochemistry could render grading more robust. Several studies showed an association between HER2-positive DCIS and ipsilateral recurrence risk, albeit currently unclear whether this is for overall, in situ or invasive recurrence. HER2-positive DCIS tends to be larger, with a higher risk of involved surgical margins. HER2-positive DCIS patients benefit more from adjuvant radiotherapy: it substantially decreases the local recurrence risk after lumpectomy, without impact on overall survival. HER2-positivity in pure biopsy-diagnosed DCIS is associated with increased upstaging to invasive carcinoma after surgery. HER2 immunohistochemistry on preoperative biopsies might therefore provide useful information to surgeons, favoring wider excisions. The time seems right to consider DCIS subtype-dependent treatment, comprising appropriate local treatment for HER2-positive DCIS patients and de-escalation for hormone receptor-positive, HER2-negative DCIS patients.

Background: Recurrence after a mastectomy occurs locally or at distance. These recurrences are of importance as they have a marked impact on the survival, psychology, and morbidity of the subject who underwent the mastectomy. Aim: The present trial was carried out to evaluate distant and local recurrence after mastectomy in subjects with breast cancer, and the effect of PMRT on recurrence. Also, the impact of nodal status, hormone status, and status of margins on this recurrence was assessed. Methods: The status of the nodes including the number of nodes evaluated, number of positive nodes, and nodal grade, hormone receptors for estrogen, progesterone, and Herceptin, along with the number of Herceptin was assessed in the study. The data collected were subjected to statistical evaluation and results were formulated. Results: PMRT was received by 26 subjects (83.8%) in recurrence cases and 6 subjects (54.5%) in the non-recurrence group with a p-value of 0.380. In invasive group, the hormone receptor status was positive in 58% (n=18), 64.5% (n=20), and 16.12% (n=5) for progesterone, estrogen, and Herceptin respectively. In invasive tumors, positive margins after surgery were seen in 2 subjects (6.89%), negative, equal, close, and were seen in 65.5%, 3.44%, and 6.89% subjects respectively. Concerning node status, 0 staging was in 5% noninvasive recurrence cases, 14% invasive recurrence cases who received radiation therapy, and in 4% subjects with invasive tumors with recurrence who did not receive radiation therapy. Conclusion: The present study suggests that subjects who undergo radiation therapy after mastectomy shows lesser rates of recurrence compared to those without any post-mastectomy radiation therapy. [ABSTRACT FROM AUTHOR]

Introduction: We explored characteristics and clinical outcomes of HER2‐negative and HER2‐low metastatic breast cancers using real‐world data. Methods: We queried the National Cancer Database to identify MBC patients that were HER2‐low or HER2‐negative per immunohistochemical staining. A binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA) and propensity‐match analysis were performed to identify correlates of survival. Results: Excluding missing data, 24,636 MBC patients diagnosed between 2008 and 2015 were identified; 27.9% were HER2‐negative and 72.1% were HER2‐low. There were no relevant demographic differences between the groups. HER2‐low tumors were half as likely to have concomitant hormone receptor‐positive status (p < 0.01). The 3‐year survival rate among hormone receptor‐negative patients was 33.8% for HER2‐low and 32.2% for HER2‐negative (p < 0.05), and 60.9% and 55.6% in HER2‐low and HER2‐negative cases among hormone receptor‐positive patients (p < 0.05), respectively. HER2‐low cases were associated with better survival on MVA (HR =0.95, 95% CI 0.91–0.99) and remained superior with propensity‐matching (HR = 0.92, 95% CI 0.89–0.96). In a subset analysis isolated to hormone receptor‐positive cases, HER2‐low remained correlated with improved survival (HR = 0.93, 95% CI 0.89–0.98) with propensity‐matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02, 95% CI 1.02–1.02) and Black race (HR = 1.26, 95% CI 1.20–1.32) [all p < 0.01]. Conclusions: In the largest such analysis performed to date, our study demonstrates a small but statistically significant association with improved survival for HER2‐low tumors compared to HER2‐negative tumors in MBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer, especially in Asia, is on the rise. With improvements in tailored treatment, needs for more individualized subtyping are increasing. This retrospective study aimed to compare human epidermal growth factor receptor 2 (HER2)-low and HER2-0 breast cancers in hormone receptor (HR)-positive patients and investigate how it affect patients. We reviewed over 10,000 breast cancer cases, focusing on strong HR-positive subtypes. HER2-low breast cancer patients tended to have better oncologic outcomes compared to HER2-0 patients. Importantly, this difference was more pronounced in postmenopausal patients. This research highlights the need for reevaluating how we classify breast cancer subtypes. Understanding these distinctions could potentially lead to more tailored treatments for patients with HER2-low breast cancer in the future. Breast cancer is a prevalent malignancy with increasing incidence, particularly in Asian countries. Classification based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is pivotal in determining treatment. Recent advances have challenged the traditional dichotomy in HER2 classification, prompting investigation into the HER2-low subtype's characteristics and outcomes. This retrospective study analyzed 10,186 non-metastatic hormone receptor (HR)-positive, HER2-negative breast cancer cases treated from 2008 to 2020. Data encompassed clinical, pathological, and treatment information. Oncologic outcomes included disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS). In total, 56.5% were HER2-low cases. Differences in patient characteristics were noted, with more BRCA1/2 mutations and higher mastectomy rates in the HER2-low group (p = 0.002, p < 0.001, respectively). Fewer received adjuvant chemotherapy or radiation therapy, and fewer histologic and nuclear grade 1 tumors were identified (all p < 0.001). With a median follow-up of 64 months (range: 13–174), HER2-low cases exhibited better DFS, OS, and BCSS than HER2-0 cases (p = 0.012, p = 0.013, and p = 0.013, respectively). Notably, the prognosis differed between premenopausal and postmenopausal subgroups, with BCSS benefitting premenopausal patients (p = 0.047) and DFS and OS benefitting postmenopausal patients in the HER2-low group (p = 0.004, p = 0.009, respectively). Multivariate analysis confirmed HER2 status as an independent predictor of these outcomes (p = 0.010, p = 0.008, and p = 0.014, respectively). This extensive single-center study elucidates the favorable prognosis associated with HER2-low status in HR-positive breast cancer. However, this effect differs among premenopausal and postmenopausal patients, necessitating further research into the underlying tumor biology. [ABSTRACT FROM AUTHOR]

Background/Objective: Hormone receptor (HR) status is one of the key factors in determining the treatment of breast cancer. Previous studies suggested that HR status may change in metastatic tissue. However, available studies focused mainly on primary biopsies and there are only few trials comparing HR status in the primary tumour and the metastasis using material from complete resection. The aim of the study was to determine the frequency of HR alterations in metastatic breast cancer. Materials and methods: The study retrospectively examines a total of 50 patients who underwent brain, lung, or liver metastasectomy for metastatic breast cancer between January 2000 and January 2019. Results: HR conversion was observed in a total of 30 cases (60.0%), while HER-2/neu (human epidermal growth factor receptor 2) discrepancy surprisingly occurred only in one case (2.0%). A change in immunophenotype occurred in 28% of cases. Triple-negativity was more frequent in brain metastases (p = 0.039). Conclusions: We have confirmed that HR conversion between the primary tumour and its metastases occurs in a significant number of cases, which has important implications for further treatment decisions. [ABSTRACT FROM AUTHOR]

Background: With the introduction of investigational human epidermal growth factor receptor 2 (HER2) targeting treatments, thorough understanding of breast cancer with different HER2 expression levels is critical. The aim of this study was to compare clinicopathologic characteristics and survival of patients with metastatic breast cancer according to the level of HER2 expression. Methods: Women with distant metastatic breast cancer during 2008–2016 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO Database Network. Breast cancer samples were categorised as HER2 immunohistochemistry score 0 (IHC0), HER2-low or HER2+. Results: Among women with hormone receptor (HR) positive metastatic breast cancer (n = 989), 373 (38%) cancers were HER2 IHC0, 472 (48%) were HER2-low and 144 (15%) were HER2+. Among HR negative patients (n = 272), the proportion of HER2 IHC0, HER2-low and HER2+ was 110 (40%), 104 (38%) and 58 (21%) respectively.Within the HR + cohort, patients with HER2 IHC0 or HER2-low cancer were significantly older compared to HER2+ patients. This age difference was not seen in the HR-cohort. The localisation of distant metastases differed significantly between HER2 IHC0 or HER2-low versus HER2+ cases. Survival rates did not differ markedly by subtypes. Conclusion: Substantial proportion of patients had a HER2-low breast cancer. No clear differences in survival were found when comparing HER2 and HR status. Getting more granular insights in the level of HER2 expression and addressing HER2-low as a separate category could help to assess the impact of emerging treatment strategies. Therefore, more detailed information on HER2 expression should be routinely reported.

Evidence theory by Dempster-Shafer for determination of hormone receptor status in breast cancer samples was introduced in our previous paper. One major topic pointed out here is the link between pieces of evidence found from different origins. In this paper the challenge of selecting appropriate ways of fusing evidence, depending on the type and quality of data involved is addressed. A parameterized family of evidence combination rules, covering the full range of potential needs, from emphasizing discrepancies in the measurements to aspiring accordance, is covered. The consequences for real patient samples are shown by modeling different decision strategies. [ABSTRACT FROM AUTHOR]

Breast cancer is a prevalent malignancy with increasing incidence, particularly in Asian countries. Classification based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is pivotal in determining treatment. Recent advances have challenged the traditional dichotomy in HER2 classification, prompting investigation into the HER2-low subtype’s characteristics and outcomes. This retrospective study analyzed 10,186 non-metastatic hormone receptor (HR)-positive, HER2-negative breast cancer cases treated from 2008 to 2020. Data encompassed clinical, pathological, and treatment information. Oncologic outcomes included disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS). In total, 56.5% were HER2-low cases. Differences in patient characteristics were noted, with more BRCA1/2 mutations and higher mastectomy rates in the HER2-low group (p = 0.002, p < 0.001, respectively). Fewer received adjuvant chemotherapy or radiation therapy, and fewer histologic and nuclear grade 1 tumors were identified (all p < 0.001). With a median follow-up of 64 months (range: 13–174), HER2-low cases exhibited better DFS, OS, and BCSS than HER2-0 cases (p = 0.012, p = 0.013, and p = 0.013, respectively). Notably, the prognosis differed between premenopausal and postmenopausal subgroups, with BCSS benefitting premenopausal patients (p = 0.047) and DFS and OS benefitting postmenopausal patients in the HER2-low group (p = 0.004, p = 0.009, respectively). Multivariate analysis confirmed HER2 status as an independent predictor of these outcomes (p = 0.010, p = 0.008, and p = 0.014, respectively). This extensive single-center study elucidates the favorable prognosis associated with HER2-low status in HR-positive breast cancer. However, this effect differs among premenopausal and postmenopausal patients, necessitating further research into the underlying tumor biology.

IntroductionA Mediterranean-style dietary pattern is believed to have cancer-protective effects. We compared the prospective associations between adherence to four established Mediterranean diet indices and breast cancer risk (including total, postmenopausal, and hormone receptor positive cases) in women in the Framingham Offspring Study.MethodsThe four indices used two different approaches to measuring adherence to a Mediterranean diet: (a) scores based on the population-specific median intakes of Mediterranean diet-related foods in a given population (i.e., alternate Mediterranean Diet (aMED) index and Mediterranean Diet Score (MDS) index), and (b) scores based on compliance with recommended intakes of relevant foods from the Mediterranean diet pyramid [i.e., Mediterranean Diet (MeDiet) index and Mediterranean Style Dietary Pattern (MSDP) index]. Dietary data were derived from semiquantitative food frequency questionnaires collected in 1991-95. Participants included 1579 women aged ≤ 30 years who were free of prevalent cancer. Women were followed through 2014, and Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for various confounders.ResultsDuring a median follow-up of approximately 18 years, 87 breast cancer cases were documented. Women in the highest (vs. lowest) score category of the pyramid-based scores (i.e., MeDiet or MSDP) had approximately 45% statistically significantly lower breast cancer risks. These effects were even stronger for any hormone receptor positive cases using the MeDiet index (highest vs. lowest score categories: HR = 0.45, 95% CI: 0.22–0.90). Neither of the median intake-based scores (i.e., aMED, MDS) was associated with breast cancer risk.DiscussionOur results suggest that the methodology and the composition of Mediterranean diet indices influence their ability to assess conformity to this specific diet pattern and predict breast cancer risk.

With the introduction of investigational human epidermal growth factor receptor 2 (HER2) targeting treatments, thorough understanding of breast cancer with different HER2 expression levels is critical. The aim of this study was to compare clinicopathologic characteristics and survival of patients with metastatic breast cancer according to the level of HER2 expression. Women with distant metastatic breast cancer during 2008–2016 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO Database Network. Breast cancer samples were categorised as HER2 immunohistochemistry score 0 (IHC0), HER2-low or HER2+. Among women with hormone receptor (HR) positive metastatic breast cancer (n = 989), 373 (38%) cancers were HER2 IHC0, 472 (48%) were HER2-low and 144 (15%) were HER2+. Among HR negative patients (n = 272), the proportion of HER2 IHC0, HER2-low and HER2+ was 110 (40%), 104 (38%) and 58 (21%) respectively. Within the HR + cohort, patients with HER2 IHC0 or HER2-low cancer were significantly older compared to HER2+ patients. This age difference was not seen in the HR-cohort. The localisation of distant metastases differed significantly between HER2 IHC0 or HER2-low versus HER2+ cases. Survival rates did not differ markedly by subtypes. Substantial proportion of patients had a HER2-low breast cancer. No clear differences in survival were found when comparing HER2 and HR status. Getting more granular insights in the level of HER2 expression and addressing HER2-low as a separate category could help to assess the impact of emerging treatment strategies. Therefore, more detailed information on HER2 expression should be routinely reported. • A substantial proportion of patients had HER2-low breast cancer. • HER2 expression levels differed between the primary tumour and the metastases. • It is important to assess HER2 status in both the primary tumour and metastases. • Similar survival in HER2-low and HER2-0 BC patients, stratified for HR. [ABSTRACT FROM AUTHOR]

Breast cancer is the primary type of cancer affecting women. Patients with hormone receptor-positive cells have lower mortality rates. Both chemotherapy and hormone therapy can improve the survival rate. This study aimed to evaluate the hormonal receptor status in female breast cancer and assess the relationship with the patient's age and family history in Najaf, Iraq. A prospective study of two-hundred and fifty-one women with mastectomies (for cancers) was performed at AL Sader Medical City from January 2019 to January 2021. We collected and analyzed data regarding the age of patients, site and size of the tumor, number of pregnancies, family history, weight, smoking, and hormone receptor status. The average age of patients was 48 years, and the peak incidence was in the 40-49 age group (30.27% of patients). Of all age groups, 48.6% (122 patients) were negative for all hormone receptors (triple negative), and only 22.70% had a positive family history. The peak incidence of cancer in our study was in the 40--49 years group. A high proportion of the hormone receptors for patients were negative (triple-negative), and most patients had a negative family history. [ABSTRACT FROM AUTHOR]

Abstract Background The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women. Methods We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. We measured 10 phthalate metabolites and phthalic acid, using a sensitive liquid chromatography mass spectrometry assay on 1032 women with breast cancer (48 African Americans, 77 Latinos, 155 Native Hawaiians, 478 Japanese Americans, and 274 Whites) and 1030 matched controls. Conditional logistic regression was used to examine risk with individual metabolites and ratios of primary (MEHP, mono-2-ethylhexyl-phthalate) to secondary (MEHHP, mono(2-ethyl-5-hydroxyhexyl); MEOHP, mono(2-ethyl-5-oxohexy)) metabolites of di-2-ethylhexyl phthalate (DEHP), a widely used plasticizer. In addition, we investigated risk associations with high (∑HMWP) and low molecular weight (∑LMWP) phthalates, as well as total phthalates which included high and low molecular weight phthalates with phthalic acid (∑LMHMPA) or without phthalic acid in molar ratios (∑LMHMmolar) and adjusted for creatinine and potential confounders. Results Among all women, breast cancer risk was higher for those in tertile 2 and tertile 3 of primary to secondary metabolites of DEHP (MEHP/(MEHHP + MEOHP)) in comparison to those in tertile 1; the respective odds ratios were 1.32 (95% CI 1.04–1.68) and 1.26 (95% CI 0.96–1.66) (P trend = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA ORT3 vs T1 = 2.66, 95% CI 1.39–5.12, P trend = 0.001). In analysis by hormone receptor (HR) status, exposure above the median of ∑LMWP was associated with an increased risk of HR-positive breast cancer (OR = 1.30, 95% CI 1.05–1.60) while above the median exposure to phthalic acid was associated with an increased risk of HR-negative breast cancer (ORabove vs below median = 1.59, 95% CI 1.01–2.48). Conclusions Further investigations of suggestive associations of elevated breast cancer risk with higher ratios of primary to secondary metabolites of DEHP, and differences in risk patterns by race/ethnicity and HR status are warranted.

Evidence theory by Dempster-Shafer for determination of hormone receptor status in breast cancer samples was introduced in our previous paper. One major topic pointed out here is the link between pieces of evidence found from different origins. In this paper the challenge of selecting appropriate ways of fusing evidence, depending on the type and quality of data involved is addressed. A parameterized family of evidence combination rules, covering the full range of potential needs, from emphasizing discrepancies in the measurements to aspiring accordance, is covered. The consequences for real patient samples are shown by modeling different decision strategies.

Siling Ren,1,* Jingxian Wu,2,* Wanchun Yin,1 Qianqian Liao,1 Sailan Gong,1 Beibei Xuan,1 Xiaoling Mu1 1Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Pathology, Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this work.Correspondence: Xiaoling MuDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaEmail mxl@hospital.cqmu.edu.cnObjective: In this study, 345 patients with endometrial carcinoma (EC) were selected to investigate the correlation between ER/PR status and the EC disease-free survival (DFS) rate.Methods: The intensity and proportion of tumor cell expression of estrogen receptors and progesterone receptors (ER/PR) status of 345 postoperative tumor specimens in ECs were independently assessed semi-quantitatively by two pathologists using immunohistochemistry, the summed score ranged from 0 to 8 points was worked out by adding proportion score and intensity score based on the breast cancer hormone receptor immunohistochemical Allred scoring system. The association between DFS in ECs and ER/PR expression (intensity, proportion and summed score) was assessed using Cox regression analysis. Gene expression data were obtained from The Cancer Genome Atlas research network (TCGA).Results: According to inclusion criteria, 201 type I and 144 type II EC patients were enrolled in this study. In the univariate analysis of type I endometrial carcinoma, the intensity, proportion and summed score of ER/PR status were significantly correlated with DFS. After adjusting for factors known to significantly impact survival, the influence of ER/PR status on DFS is generally decreased but the correlation is still significant. In the univariate analysis of type II endometrial carcinoma, the intensity, proportion and summed score of ER/PR status were significantly correlated with DFS. After adjusting for factors known to significantly impact survival, the influence of ER status on DFS is generally decreased, but the correlation is still significant, the effect of PR expression on DFS is not statistically significant.Conclusion: Higher ER/PR expression status was associated with better DFS in patients with type I endometrial cancer after adjusting for known factors that significantly affect survival. In patients with type II endometrial cancer, patients with positive ER expression were significantly associated with better DFS. However, the effect of PR expression on DFS was not statistically significant.Keywords: endometrial cancer, endometrioid carcinoma, disease-free survival rate, hormone receptor status, ER, PR

Background: The association of sex hormones with receptor status and breast cancer (BC) incidence is studied with inconclusive results. The present work assessed the serum estrogen, progesterone, and testosterone concentrations and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of newly diagnosed Sri Lankan BC patients and studied the possibility of risk assessment for BC using these parameters.Methods: Serum estrogen, progesterone, and testosterone concentrations of newly diagnosed BC patients (n = 155) were assessed and compared with apparently healthy age-matched women (n = 75). Hormone concentrations were assessed with an enzyme immunoassay competition method with fluorescent detection (Biomerieux, France). Hormone receptor statuses were recorded from histopathology reports.Results: Estrogen and progesterone concentrations were not significantly different according to the menstrual phase of premenopausal BC or healthy women or according to the menopausal status. Testosterone concentration of BC patients was significantly (P = 0.001) lower than in apparently healthy women. Estrogen and progesterone concentrations were not significantly different according to ER and PR status. However, progesterone concentrations of postmenopausal were significantly different (P = 0.021) among HER2 overexpressed women when compared to HER2-negative women. Postmenopausal women with progesterone level below 0.25 ng/mL were more likely to have HER2 overexpressed (P = 0.002).Conclusions: Serum estrogen and progesterone concentrations of BC patients were not significantly different when compared with apparently healthy women. Women with testosterone level below 0.26 ng/mL demonstrated a higher risk of having BC. Serum progesterone concentrations of BC patients were significantly higher among HER2 overexpressed women compared to HER2-negative women. [ABSTRACT FROM AUTHOR]

Abstract Background Perinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer. We aimed to evaluate the association between young-onset breast cancer and perinatal exposures and to explore etiologic heterogeneity in the relationship between associated perinatal factors and estrogen receptor status of the tumor. Methods We addressed this in a sister-matched case-control study. Cases were women who had been diagnosed with ductal carcinoma in situ or invasive breast cancer before the age of 50. Each case had a sister control who was free of breast cancer up to the same age at which her case sister developed the disease. The factors considered were self-reported and included the mother’s preeclampsia in that pregnancy, mother’s smoking in that pregnancy, gestational hypertension, prenatal diethylstilbestrol use, and gestational diabetes, as well as low birth weight (less than 5.5 pounds), high birth weight (greater than 8.8 pounds), short gestational length (less than 38 completed weeks), and being breastfed or being fed soy formula. Results In conditional logistic regression analyses, high birth weight (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.07–2.36) and preeclampsia (adjusted OR = 1.92, CI 0.824–4.5162) were positively associated with risk. The association with preeclampsia was stronger when the analysis was restricted to invasive breast cancer (OR = 2.87, CI 1.08–7.59). We also used case-only analyses to assess etiologic heterogeneity for estrogen receptor (ER)-positive versus estrogen receptor-negative cancer. Women who were born to a preeclamptic pregnancy and later developed young-onset breast cancer were at increased odds for the ER-negative type (OR = 2.27; CI 1.05–4.92). Conclusion These results suggest that being born to a preeclamptic pregnancy may increase risk for young-onset breast cancer, especially for the ER-negative subtype.

Abstract Background The presence of tumor-infiltrating lymphocytes has been associated with prognosis and chemotherapy response, particularly in high-risk breast cancer subtypes. There is limited data so far as to (i) how tumor-infiltrating lymphocyte (TIL) measurements correlate with genomic measurements such as the Oncotype DX Recurrence Score® and (ii) whether the survival impact of TIL measurements varies according to different adjuvant systemic therapies. Methods The WSG PlanB trial compared an anthracycline-free chemotherapy regimen (6x docetaxel/cyclophosphamide, TC) to an anthracycline-taxane sequence (4xEC followed by 4x docetaxel) in patients with intermediate-risk, HER2-negative early breast cancer (EBC). Patients with HR-positive HER2-negative EBC were further stratified to receive endocrine therapy alone vs. chemotherapy followed by endocrine therapy based on Recurrence Score results and nodal status. In this analysis, three independent observers quantified and categorized the presence of TILs among tumor samples from patients in PlanB. TIL measurements were correlated with clinical/pathological parameters and treatment outcome overall and according to the treatment arm. Results Disease-free survival (DFS) rates were significantly better (p = .04) in HR-negative patients with high vs. intermediate TIL levels and were higher in low vs. intermediate TIL patients, however with borderline significance only (p = .06). There were no significant differences among TIL categories in HR+ patients. High RS categories, HR-negative status, and high KI67 were independently and significantly associated with high TIL categories. There was no significant impact of TIL category on DFS in patients treated by endocrine therapy only; however, in patients receiving chemotherapy, DFS in the intermediate TIL category was lower than that in the other categories. Conclusion Although the presence of high TILs is associated with negative prognostic parameters such as high KI67 and HR-negative status among patients with HR-positive HER2-negative EBC, patients with high TILs show a favorable 5-year DFS in both HR-positive/HER2-negative and triple-negative breast cancer.

Purpose: Breast cancer is the most frequent cancer in women, with significant mortality. Mammography is a routine investigation for breast disease. A known risk factor for breast cancer is increased breast density. Here, we tried to observe if mammographic density also affects the hormone receptor status of breast cancer, which will help in the understanding of the biological mechanisms of breast cancer development., Material and Methods: Suspected breast cancer patients at Lok Nayak Hospital, Delhi, underwent mammography in the Department of Radiodiagnosis. The density of breast contralateral to the mass was assessed using Hologic Quantra software version 2.1.1 [Area Breast Density(ABD)]. The hormone receptor status of all the tumours was recorded on histopathology. Of these, 100 confirmed cases were included in the study., Results: ER-positive, PR-positive, and HER2-positive tumours were seen in 41%, 33%, and 34% patients, respectively. Regarding ER receptor status, the mean ABD for positive and negative tumours was 27% and 23%, respectively, p -value = 0.01, showing significant relation between them. Mean ABD for HER2-positive and -negative tumours was 25% and 24%, respectively, p -value = 0.75. Mean ABD for PR-positive and PR-negative tumours was 23% and 25%, respectively, p -value = 0.42 (not significant)., Conclusions: We found that ER-positive tumours were common in dense breasts, which was statistically significant. However, this was not true for PR and HER2 receptor status. Limited studies have been done to study MD using computerised software and its effect on hormone receptor status, with conflicting results. Further, large, multicentric studies can be useful in understanding the mechanism and providing better treatment for breast cancer patients., (© Pol J Radiol 2024.)

Background: A rare subtype of breast cancer, atypical medullary carcinoma of the breast (AMCB), shows a highly adverse prognosis compared to medullary carcinoma of the breast (MBC). The current study aimed to establish a correlated nomogram for the identification of the prognostic factors of AMCB and MBC. Methods: Kaplan–Meier and Cox regression analyses were applied to data acquired from the Surveillance, Epidemiology and End Results (SEER) database for 2004 to 2013 to analyse tumour characteristics and overall survival. Propensity score matching (PSM) analysis was performed to determine the overall survival (OS) among those with AMCB and MBC. A predictive nomogram was created, and the concordance index (C-index) was used to predict accuracy and discriminative ability. Results: A total of 2,001 patients from the SEER database were diagnosed with MBC between 2004 and 2013, including 147 patients diagnosed with AMCB. The number of diagnoses gradually increased in both groups. Cox analysis of multivariate and Kaplan–Meier analysis showed that older age (HR = 3.005, 95% CI 1.906–4.739) and later stage were significantly associated with poor prognosis, while cancer-directed surgery was an independent protective factor (HR = 0.252, 95% CI 0.086–0.740). In the HR-negative stratification analysis, older age (HR = 2.476, 95% CI 1.398–4.385), later stage and histological type (HR=0.381, 95% CI 0.198-0.734) were found to be independent prognostic factors for low standard survival. The log-rank analysis demonstrated significantly worse prognostic factors for patients with AMCB than for those with MBC (P = 0.004). A nomogram (C-index for survival = 0.75; 95% CI 0.69–0.81) was established from four independent prognostic factors after complete identification. Conclusions: MBC is rare, and cancer-directed surgery, older age, and later stage are independently linked with prognosis. In the HR negative population, AMCB patients show a worse survival gain than those with MBC. [ABSTRACT FROM AUTHOR]

BackgroundA rare subtype of breast cancer, atypical medullary carcinoma of the breast (AMCB), shows a highly adverse prognosis compared to medullary carcinoma of the breast (MBC). The current study aimed to establish a correlated nomogram for the identification of the prognostic factors of AMCB and MBC.MethodsKaplan–Meier and Cox regression analyses were applied to data acquired from the Surveillance, Epidemiology and End Results (SEER) database for 2004 to 2013 to analyse tumour characteristics and overall survival. Propensity score matching (PSM) analysis was performed to determine the overall survival (OS) among those with AMCB and MBC. A predictive nomogram was created, and the concordance index (C-index) was used to predict accuracy and discriminative ability.ResultsA total of 2,001 patients from the SEER database were diagnosed with MBC between 2004 and 2013, including 147 patients diagnosed with AMCB. The number of diagnoses gradually increased in both groups. Cox analysis of multivariate and Kaplan–Meier analysis showed that older age (HR = 3.005, 95% CI 1.906–4.739) and later stage were significantly associated with poor prognosis, while cancer-directed surgery was an independent protective factor (HR = 0.252, 95% CI 0.086–0.740). In the HR-negative stratification analysis, older age (HR = 2.476, 95% CI 1.398–4.385), later stage and histological type (HR=0.381, 95% CI 0.198-0.734) were found to be independent prognostic factors for low standard survival. The log-rank analysis demonstrated significantly worse prognostic factors for patients with AMCB than for those with MBC (P = 0.004). A nomogram (C-index for survival = 0.75; 95% CI 0.69–0.81) was established from four independent prognostic factors after complete identification.ConclusionsMBC is rare, and cancer-directed surgery, older age, and later stage are independently linked with prognosis. In the HR negative population, AMCB patients show a worse survival gain than those with MBC.

Background: Benzo[a]pyrene (BaP) is an endocrine-disrupting pollutant formed during incomplete combustion of organic materials. It has been recognized as a reproductive and developmental toxicant, however epidemiological evidence of the long-term effect of ambient air BaP on breast cancer (BC) is limited. Thus we evaluated associations between ambient air BaP exposure and risk of BC, overall and according to menopausal status and molecular subtypes (estrogen receptor negative/positive (ER−/ER+) and progesterone receptor negative/positive (PR−/PR+)), stage and grade of differentiation of BC in the French E3N cohort study. Methods: Within a nested case-control study of 5222 incident BC cases and 5222 matched controls, annual BaP exposure was estimated using a chemistry-transport model (CHIMERE) and was assigned to the geocoded residential addresses of participants for each year during the 1990–2011 follow-up period. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Overall, cumulative airborne BaP exposure was significantly associated with the overall risk of BC, for each 1 interquartile range (IQR) increase in the concentration levels of BaP (1.42 ng/m3), the OR = 1.15 (95% CI: 1.04–1.27). However, by menopausal status, the significant positive association remained only in women who underwent menopausal transition (i.e. premenopausal women at inclusion who became postmenopausal at diagnosis), OR per 1 IQR = 1.20 (95% CI: 1.03–1.40). By hormone receptor status, positive associations were observed for ER+, PR + and ER + PR + BC, with ORs = 1.17 (95% CI: 1.04–1.32), 1.16 (95% CI: 1.01–1.33), and 1.17 (95% CI: 1.01–1.36) per 1 IQR, respectively. There was also a borderline positive association between BaP and grade 3 BC (OR per 1 IQR = 1.15 (95% CI: 0.99–1.34). Conclusions: We provide evidence of increased risk of BC associated with cumulative BaP exposure, which varied according to menopausal status, hormone receptor status, and grade of differentiation of BC. Our results add further epidemiological evidence to the previous experimental studies suggesting the adverse effects of BaP.

Background: The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women.Methods: We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. We measured 10 phthalate metabolites and phthalic acid, using a sensitive liquid chromatography mass spectrometry assay on 1032 women with breast cancer (48 African Americans, 77 Latinos, 155 Native Hawaiians, 478 Japanese Americans, and 274 Whites) and 1030 matched controls. Conditional logistic regression was used to examine risk with individual metabolites and ratios of primary (MEHP, mono-2-ethylhexyl-phthalate) to secondary (MEHHP, mono(2-ethyl-5-hydroxyhexyl); MEOHP, mono(2-ethyl-5-oxohexy)) metabolites of di-2-ethylhexyl phthalate (DEHP), a widely used plasticizer. In addition, we investigated risk associations with high (∑HMWP) and low molecular weight (∑LMWP) phthalates, as well as total phthalates which included high and low molecular weight phthalates with phthalic acid (∑LMHMPA) or without phthalic acid in molar ratios (∑LMHMmolar) and adjusted for creatinine and potential confounders.Results: Among all women, breast cancer risk was higher for those in tertile 2 and tertile 3 of primary to secondary metabolites of DEHP (MEHP/(MEHHP + MEOHP)) in comparison to those in tertile 1; the respective odds ratios were 1.32 (95% CI 1.04-1.68) and 1.26 (95% CI 0.96-1.66) (Ptrend = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA ORT3 vs T1 = 2.66, 95% CI 1.39-5.12, Ptrend = 0.001). In analysis by hormone receptor (HR) status, exposure above the median of ∑LMWP was associated with an increased risk of HR-positive breast cancer (OR = 1.30, 95% CI 1.05-1.60) while above the median exposure to phthalic acid was associated with an increased risk of HR-negative breast cancer (ORabove vs below median = 1.59, 95% CI 1.01-2.48).Conclusions: Further investigations of suggestive associations of elevated breast cancer risk with higher ratios of primary to secondary metabolites of DEHP, and differences in risk patterns by race/ethnicity and HR status are warranted. [ABSTRACT FROM AUTHOR]

Abstract Background The association between oral contraceptive (OC) use and long-term mortality remains uncertain and previous studies have reported conflicting findings. We aim to assess the long-term impact of OC use on all-cause and cancer-specific mortality. Methods Out of 49,259 participants, we analysed data on 2120 (4.3%) women diagnosed with first primary breast cancer between 1993 and 2012, in the Swedish Women’s Lifestyle and Health Study. Kaplan–Meier plots were used to graph the hazard of mortality in association with oral contraceptives use, stage of disease and hormone receptors status at diagnosis. Cox proportional hazard model were used to estimate hazard ratios (HR) between OC use and all-cause mortality. The same association was studied for breast cancer-specific mortality by modelling the log cumulative mortality risk, adjusting for clinical stage at diagnosis, hormone receptor status, body mass index and smoking. Results Among 2120 women with breast cancer, 1268 (84%) reported ever use of OC and 254 died within 10 years of diagnosis. The risk of death for OC ever-users relative to never-users was: HR = 1.13 (95% CI: 0.66–1.94) for all-cause mortality and HR = 1.29 (95% CI: 0.53–3.18) for breast cancer-specific mortality. A high percentage of women (42.9%) were diagnosed at early stage disease (stage I). Conclusions Among women with primary breast cancer, OC ever-users compared to never- users did not have a higher all-cause or breast cancer specific-mortality, after the adjustment of risk factors.

Background/Aim: The aim of this study was to determine the importance of surgical treatment, utility of hormone receptor status and selected biomarkers in the prognosis of patients with liver metastases from breast cancer (BCLM). Patients and Methods: Thirty female underwent surgery for BCLM between 1/2000 and 1/2019. Results: The type of surgery (resection/radiofrequency ablation) had no impact on overall survival (OS) - (p=0.894). Having more than one BCLM (p=0.003), expression of human epidermal receptor 2 in metastases (p=0.034), as well as an elevated presurgical level of carbohydrate antigen 19-9 (p=0.017) and postsurgical thymidine kinase (p=0.034) were negative prognostics factor for recurrence-free survival. The factors affecting OS included the number of liver procedures (p=0.021), the degree of proliferative activity (p=0.008) and elevated postsurgical carcinoembryonic antigen level (p=0.038). Conclusion: The type of surgery had no impact on OS. Markers and hormonal status of liver metastases are important factors affecting prognosis. [ABSTRACT FROM AUTHOR]

Background/objective: Hormone receptor (HR) status is one of the key factors in determining the treatment of breast cancer. Previous studies suggested that HR status may change in metastatic tissue. However, available studies focused mainly on primary biopsies and there are only few trials comparing HR status in the primary tumour and the metastasis using material from complete resection. The aim of the study was to determine the frequency of HR alterations in metastatic breast cancer., Materials and Methods: The study retrospectively examines a total of 50 patients who underwent brain, lung, or liver metastasectomy for metastatic breast cancer between January 2000 and January 2019., Results: HR conversion was observed in a total of 30 cases (60.0%), while HER-2/neu (human epidermal growth factor receptor 2) discrepancy surprisingly occurred only in one case (2.0%). A change in immunophenotype occurred in 28% of cases. Triple-negativity was more frequent in brain metastases (p = 0.039)., Conclusions: We have confirmed that HR conversion between the primary tumour and its metastases occurs in a significant number of cases, which has important implications for further treatment decisions., Competing Interests: Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Greater Poland Cancer Centre.)

PURPOSE: To evaluate how the association between body size and breast cancer risk varies by tumor receptor subtype, host factors, and other exposures among women in the California Teachers Study cohort. METHODS: Among 52,642 postmenopausal women, 2,321 developed invasive breast cancer with known estrogen- and progesterone-receptor status (1,652 ER+PR+, 338 ER+PR-, and 312 ER-PR-) between 1995 and 2007. In a subset of 35,529 with waist circumference data, 1,377 developed invasive breast cancer with known ERPR status (991 ER+PR+, 208 ER+PR-, 169 ER-PR-) between 1997 and 2007. Multivariate Cox regression was performed to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS: Obesity, adult weight gain of ≥40 pounds, greater abdominal adiposity, and greater height increased the risk of ER+PR+ breast cancer. The increased risk associated with postmenopausal obesity was limited to those who did not use hormone therapy (HT) at cohort entry (RR = 1.37; 95% CI, 1.05-1.78 for BMI ≥ 30 vs.

Goals: BRCA1/2 mutations are associated with bilateral breast cancer. The extent of concordance between synchronous bilateral breast cancer (SBBC) tumors with respect to hormone receptor expression and BRCA1/2 mutations is unknown. We investigated the distribution of BRCA1/2 mutations and bilateral estrogen receptor (ER) status in SBBC.Methods: A retrospective analysis was performed on 15,337 patients with primary breast cancer who underwent surgical treatment at the Fudan University Shanghai Cancer Center between 2007 and 2014. We included 163 patients with synchronous bilateral breast cancer who had germline BRCA1/2 mutations testing. BRCA1/2 pathogenic/likely pathogenic mutations and other clinicopathological characteristics were studied in further analyses.Results: Patients with SBBC developed breast cancer at an older age and had a higher rate of ER positivity than patients with UBC (p < 0.001, separately). In contrast, 14.1% of SBBC patients had carcinomas with a lobular component in either breast based on pathological reports (p < 0.001). Twelve patients had BRCA1 mutations, and 14 patients had BRCA2 mutations, while no patients had mutations in both genes. The BRCA1/2 mutation rate was higher in younger patients (23.4 vs. 11.1%, p = 0.036). SBBC patients with a family history of breast cancer or bilateral ER-negative disease had a higher frequency of BRCA1/2 mutations than the cohort without a history of these conditions. SBBC with a bilateral ER-discordant status had a very low frequency of BRCA1/2 mutations (5.6%). Patients with an ER-positive (concordant or discordant) status had better 3-year disease-free survival than patients with a concordant ER-negative status (HR = 0.324, 95% CI: 0.126–0.837, P = 0.020). However, the outcomes were similar during long-term follow-up. Pathological lymph node stage was the only prognostic factor for SBBC in both univariate and multivariate Cox analyses.Conclusions: Our study shows that Chinese women with SBBC have different characteristics from their UBC counterparts. SBBC patients with a younger age, family history of breast cancer, or bilateral ER-negative disease are more likely to have BRCA1/2 mutations. SBBC patients with a concordant ER-negative status had worse early outcomes. Our results suggest that there may be additional factors underlying the tumor biology and genetics of SBBC.

Background: Perinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer. We aimed to evaluate the association between young-onset breast cancer and perinatal exposures and to explore etiologic heterogeneity in the relationship between associated perinatal factors and estrogen receptor status of the tumor.Methods: We addressed this in a sister-matched case-control study. Cases were women who had been diagnosed with ductal carcinoma in situ or invasive breast cancer before the age of 50. Each case had a sister control who was free of breast cancer up to the same age at which her case sister developed the disease. The factors considered were self-reported and included the mother's preeclampsia in that pregnancy, mother's smoking in that pregnancy, gestational hypertension, prenatal diethylstilbestrol use, and gestational diabetes, as well as low birth weight (less than 5.5 pounds), high birth weight (greater than 8.8 pounds), short gestational length (less than 38 completed weeks), and being breastfed or being fed soy formula.Results: In conditional logistic regression analyses, high birth weight (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.07-2.36) and preeclampsia (adjusted OR = 1.92, CI 0.824-4.5162) were positively associated with risk. The association with preeclampsia was stronger when the analysis was restricted to invasive breast cancer (OR = 2.87, CI 1.08-7.59). We also used case-only analyses to assess etiologic heterogeneity for estrogen receptor (ER)-positive versus estrogen receptor-negative cancer. Women who were born to a preeclamptic pregnancy and later developed young-onset breast cancer were at increased odds for the ER-negative type (OR = 2.27; CI 1.05-4.92).Conclusion: These results suggest that being born to a preeclamptic pregnancy may increase risk for young-onset breast cancer, especially for the ER-negative subtype. [ABSTRACT FROM AUTHOR]

Background: The presence of tumor-infiltrating lymphocytes has been associated with prognosis and chemotherapy response, particularly in high-risk breast cancer subtypes. There is limited data so far as to (i) how tumor-infiltrating lymphocyte (TIL) measurements correlate with genomic measurements such as the Oncotype DX Recurrence Score® and (ii) whether the survival impact of TIL measurements varies according to different adjuvant systemic therapies.Methods: The WSG PlanB trial compared an anthracycline-free chemotherapy regimen (6x docetaxel/cyclophosphamide, TC) to an anthracycline-taxane sequence (4xEC followed by 4x docetaxel) in patients with intermediate-risk, HER2-negative early breast cancer (EBC). Patients with HR-positive HER2-negative EBC were further stratified to receive endocrine therapy alone vs. chemotherapy followed by endocrine therapy based on Recurrence Score results and nodal status. In this analysis, three independent observers quantified and categorized the presence of TILs among tumor samples from patients in PlanB. TIL measurements were correlated with clinical/pathological parameters and treatment outcome overall and according to the treatment arm.Results: Disease-free survival (DFS) rates were significantly better (p = .04) in HR-negative patients with high vs. intermediate TIL levels and were higher in low vs. intermediate TIL patients, however with borderline significance only (p = .06). There were no significant differences among TIL categories in HR+ patients. High RS categories, HR-negative status, and high KI67 were independently and significantly associated with high TIL categories. There was no significant impact of TIL category on DFS in patients treated by endocrine therapy only; however, in patients receiving chemotherapy, DFS in the intermediate TIL category was lower than that in the other categories.Conclusion: Although the presence of high TILs is associated with negative prognostic parameters such as high KI67 and HR-negative status among patients with HR-positive HER2-negative EBC, patients with high TILs show a favorable 5-year DFS in both HR-positive/HER2-negative and triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Goals: BRCA1/2 mutations are associated with bilateral breast cancer. The extent of concordance between synchronous bilateral breast cancer (SBBC) tumors with respect to hormone receptor expression and BRCA1/2 mutations is unknown. We investigated the distribution of BRCA1/2 mutations and bilateral estrogen receptor (ER) status in SBBC. Methods: A retrospective analysis was performed on 15,337 patients with primary breast cancer who underwent surgical treatment at the Fudan University Shanghai Cancer Center between 2007 and 2014. We included 163 patients with synchronous bilateral breast cancer who had germline BRCA1/2 mutations testing. BRCA1/2 pathogenic/likely pathogenic mutations and other clinicopathological characteristics were studied in further analyses. Results: Patients with SBBC developed breast cancer at an older age and had a higher rate of ER positivity than patients with UBC (p < 0.001, separately). In contrast, 14.1% of SBBC patients had carcinomas with a lobular component in either breast based on pathological reports (p < 0.001). Twelve patients had BRCA1 mutations, and 14 patients had BRCA2 mutations, while no patients had mutations in both genes. The BRCA1/2 mutation rate was higher in younger patients (23.4 vs. 11.1%, p = 0.036). SBBC patients with a family history of breast cancer or bilateral ER-negative disease had a higher frequency of BRCA1/2 mutations than the cohort without a history of these conditions. SBBC with a bilateral ER-discordant status had a very low frequency of BRCA1/2 mutations (5.6%). Patients with an ER-positive (concordant or discordant) status had better 3-year disease-free survival than patients with a concordant ER-negative status (HR = 0.324, 95% CI: 0.126–0.837, P = 0.020). However, the outcomes were similar during long-term follow-up. Pathological lymph node stage was the only prognostic factor for SBBC in both univariate and multivariate Cox analyses. Conclusions: Our study shows that Chinese women with SBBC have different characteristics from their UBC counterparts. SBBC patients with a younger age, family history of breast cancer, or bilateral ER-negative disease are more likely to have BRCA1/2 mutations. SBBC patients with a concordant ER-negative status had worse early outcomes. Our results suggest that there may be additional factors underlying the tumor biology and genetics of SBBC. [ABSTRACT FROM AUTHOR]

Breast cancer prognosis and administration of therapies are aided by knowledge of hormonal and HER2 receptor status. Breast cancer lacking estrogen receptors, progesterone receptors and HER2 receptors are difficult to treat. Regarding large data repositories such as The Cancer Genome Atlas, available wet-lab methods for establishing the presence of these receptors do not always conclusively cover all available samples. To this end, we introduce median-supplement methods to identify hormonal and HER2 receptor status phenotypes of breast cancer patients using gene expression profiles. In these approaches, supplementary instances based on median patient gene expression are introduced to balance a training set from which we build simple models to identify the receptor expression status of patients. In addition, for the purpose of benchmarking, we examine major machine learning approaches that are also applicable to the problem of finding receptor status in breast cancer. We show that our methods are robust and have high sensitivity with extremely low false-positive rates compared with the well-established methods. A successful application of these methods will permit the simultaneous study of large collections of samples of breast cancer patients as well as save time and cost while standardizing interpretation of outcomes of such studies. [ABSTRACT FROM AUTHOR]

Objective:Socioeconomic and cultural factors influence breast cancer prognosis. The effect of these factors on breast cancer was evaluated among women who live in Gaziantep and its surroundings.Materials and Methods:female patients who were admitted to Gaziantep University Oncology Hospital with a diagnosis of breast cancer between October 2006-July 2013 were included in the study. The effects of socio-demographic characteristics on clinical-pathological features were evaluated.Results:The mean age of 813 women was 48.8 years. The majority were premenopausal women. Advanced stage disease on diagnosis was detected more in our region. The rate of breast cancer with unfavorable prognostic features was higher among patients who were illiterate, with low economic income and residing in rural areas.Conclusion:Socioeconomic-cultural factors influence the biology and clinical course of breast cancer among women who live in Gaziantep province.

Identification of circulating tumor cells (CTCs) by surface marker expression and ploidy analysis [immunostaining-fluorescence in situ hybridization (iFISH)] has been shown to be a highly sensitive method in the identification of certain solid cancers. In the present study, iFISH analysis was performed to identify CTCs in 184 patients with newly diagnosed non-metastatic breast cancer, and the distribution of CTC subtypes was characterized based on cytokeratin (CK) expression and ploidy status. It was revealed that CTCs of non-metastatic, aneuploid breast cancers, independent of CK expression profile, can be detected with high sensitivity (90.76%) by the iFISH system. Higher CTC counts and sensitivity were observed in patients with increased tumor size burden and unfavorable hormone receptor status. Investigation of CTC subtypes based on ploidy analysis indicated that triploid CTCs constituted the majority of CTCs evaluated. While CK-positive CTCs were detected in a small cohort of patients, an overall low rate of CK expression was observed in the 18 patient samples evaluated. Of note, CK expression was rare in CTCs detected in patients with Herceptin 2 (Her2)-positive or triple-negative [estrogen receptor (ER)-, progesterone receptor (PR)- and Her2-negative], indicating that lack of ER and PR may result in promotion of epithelial-mesenchymal transition and enhancement of tumor aggression. [ABSTRACT FROM AUTHOR]

Nitrogen dioxide (NO 2) is an important air pollutant due to its adverse effects on human health. Yet, current evidence on the association between NO 2 and the risk of breast cancer lacks consistency. In this study, we investigated the association between long-term exposure to NO 2 and breast cancer risk in the French E3N cohort study. Association of breast cancer risk with NO 2 exposure was assessed in a nested case-control study within the French E3N cohort including 5222 breast cancer cases identified over the 1990–2011 follow-up period and 5222 matched controls. Annual mean concentrations of NO 2 at participants' residential addresses for each year from recruitment 1990 through 2011, were estimated using a land use regression (LUR) model. Multivariable conditional logistic regression models were used to compute odds ratios (ORs) and their 95% confidence intervals (CIs). Additional analyses were performed using NO 2 concentrations estimated by CHIMERE, a chemistry transport model. Overall, the mean NO 2 exposure was associated with an increased risk of breast cancer. In all women, for each interquartile range (IQR) increase in NO 2 levels (LUR: 17.8 μg/m3), the OR of the model adjusted for confounders was 1.09 (95% CI: 1.01–1.18). The corresponding OR in the fully adjusted model (additionally adjusted for established breast cancer risk factors) was 1.07 (95% CI: 0.98–1.15). By menopausal status, results for postmenopausal women were comparable to those for all women, while no association was observed among premenopausal women. By hormone receptor status, the OR of estrogen receptor positive breast cancer = 1.07 (95% CI: 0.97–1.19) in the fully adjusted model. Additional analyses using the CHIMERE model showed slight differences in ORs estimates. The results of this study indicate an increased risk of breast cancer associated with long-term exposure to NO 2 air pollution. Observing comparable effects of NO 2 exposure estimated by two different models, reinforces these findings. [Display omitted] • NO 2 levels were estimated over a 22 years period, by two exposure assessment models. • Breast cancer risk was increased in association with exposure to NO 2 air pollution. • By menopausal status, the associations appear to be limited to postmenopausal women. • NO 2 air pollution was positively associated with risk of ER + breast cancer. • Consistent associations were observed for the two exposure assessment methods. [ABSTRACT FROM AUTHOR]

This review is devoted to a comparative analysis of receptor status, immunity, angiogenesis, metastatic mammal glands cancer expression profiling in humans and animals. Angiogenesis has been assessed by quantitative and immunohistochemical characteristics by means of evaluation of microvascular density (MVD) using Claudin-5 (CLDN-5) as a marker of vascular endothelium in tumors of mammary glands in dogs.

Background: Immunohistochemical assessment of the hormone receptor status of breast carcinoma is a routine investigation. However, there is no worldwide consensus on the scoring system. The Quick Score is claimed to be a reliable scoring system, which assesses both the proportion of stained cells and the intensity of staining. Aims: To assess the value of Quick Score in terms of accepted clinicopathological parameters and to document the prevalence of hormone receptor-positive breast carcinomas in the study sample. Materials and Methods: Clinicopathological parameters of 151 breast cancers were compared with the Quick Scores for estrogen receptor (ER) and progesterone receptor (PR) status. Results and Conclusions: The Quick Score for ER was 0 in 54.3% (82/151) and for PR was 0 in 51.7% (75/145), indicating no hormone receptor expression in the majority. The Nottingham grade and the mitotic count had a significant inverse relationship with the Quick Score for hormone receptor status. The Nottingham Prognostic Index (NPI) also had an inverse relationship with the hormone receptor status.

Introduction: A Mediterranean-style dietary pattern is believed to have cancer-protective effects. We compared the prospective associations between adherence to four established Mediterranean diet indices and breast cancer risk (including total, postmenopausal, and hormone receptor positive cases) in women in the Framingham Offspring Study., Methods: The four indices used two different approaches to measuring adherence to a Mediterranean diet: (a) scores based on the population-specific median intakes of Mediterranean diet-related foods in a given population (i.e., alternate Mediterranean Diet (aMED) index and Mediterranean Diet Score (MDS) index), and (b) scores based on compliance with recommended intakes of relevant foods from the Mediterranean diet pyramid [i.e., Mediterranean Diet (MeDiet) index and Mediterranean Style Dietary Pattern (MSDP) index]. Dietary data were derived from semiquantitative food frequency questionnaires collected in 1991-95. Participants included 1579 women aged ≤ 30 years who were free of prevalent cancer. Women were followed through 2014, and Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for various confounders., Results: During a median follow-up of approximately 18 years, 87 breast cancer cases were documented. Women in the highest (vs. lowest) score category of the pyramid-based scores (i.e., MeDiet or MSDP) had approximately 45% statistically significantly lower breast cancer risks. These effects were even stronger for any hormone receptor positive cases using the MeDiet index (highest vs. lowest score categories: HR = 0.45, 95% CI: 0.22-0.90). Neither of the median intake-based scores (i.e., aMED, MDS) was associated with breast cancer risk., Discussion: Our results suggest that the methodology and the composition of Mediterranean diet indices influence their ability to assess conformity to this specific diet pattern and predict breast cancer risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yiannakou, Singer and Moore.)

Objectives: Trastuzumab, a humanized monoclonal antibody that binds human epidermal growth factor receptor 2 (HER2), dramatically improves the clinical outcomes of HER2- positive breast cancer. Emerging evidence implied that the clinical behavior and sensitivity to targeted agents in HER2-positive breast cancer differed by hormone receptor (HR) status. The objective of this study was to determine the effect of the HR status on survival benefit of HER2-positive metastatic breast cancer when treated with anti-HER2-targeted therapy in People's Republic of China. Methods: Metastatic breast cancer patients with HER2-positive diseases across six cancer centers in People's Republic of China were retrospectively analyzed in our study. Patients were classified intofour groups according to HR/HER2 status and trastuzumab treatment: HER2+/ HR+ patients with first-line trastuzumab treatment, HER2+/HR+ patients with no trastuzumab treatment, HER2+/HR- patients with first-line trastuzumab treatment, and HER2+/HR- patients with no trastuzumab treatment. Kaplan-Meier analysis, log-rank test, and multivariate analysis were performed during analysis. Results: A total of 295 patients were included in the final analysis. The median overall survival was 30 months (95% confidence interval: 27.521-32.479). Among patients with HER2+/ HR- disease, significant survival benefit was observed when treated with trastuzumab (30 vs 21 months, P=0.000). However, in patients with HER2+/HR+ disease, trastuzumab administration had a survival improvement trend but no significant statistical differences (36 vs 30 months, P=0.258). In the multivariate analysis, HR status was an independent predictor of overall survival and trastuzumab treatment had significantly decreased risk of death in HER2+/ HR- patients (hazard ratio =0.330). Conclusion: HR status is an independent predictor of overall survival in HER2-positive metastatic breast cancer patients and patients with HER2+/HR- subtype might be associated with more survival benefits when treated with trastuzumab-based regimens. [ABSTRACT FROM AUTHOR]

ntroduction: The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer. Material and methods: A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis. Results: During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR- patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer. Conclusions: These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor. [ABSTRACT FROM AUTHOR]

The correlation between histologic grade, an increasingly important measure of prognosis for patients with breast cancer, and tryptophan levels from tissues of 15 breast carcinoma patients was investigated. Changes in the relative content of key native organic biomolecule tryptophan were seen from the fluorescence spectra of cancerous and paired normal tissues with excitation wavelengths of 280 and 300 nm. Due to a large spectral overlap and matching excitation--emission spectra, fluorescence resonance energy transfer from tryptophan-donor to reduced nicotinamide adenine dinucleotides-acceptor was noted. We used the ratios of fluorescence intensities at their spectral emission peaks, or spectral fingerprint peaks, at 340, 440, and 460 nm. Higher ratios correlated strongly with high histologic grade, while lower-grade tumors had low ratios. Large tumor size also correlated with high ratios, while the number of lymph node metastases, a major factor in staging, was not correlated with tryptophan levels. High histologic grade correlates strongly with increased content of tryptophan in breast cancer tissues and suggests that measurement of tryptophan content may be useful as a part of the evaluation of these patients. [ABSTRACT FROM AUTHOR]

Background The procoagulant state in cancer increases the thrombotic risk, but also supports tumor progression. To investigate the molecular mechanisms controlling cancer and hemostasis, we conducted a case-control study of genotypic and phenotypic variables of the tissue factor (TF) pathway of coagulation in breast cancer. Methods 366 breast cancer patients and 307 controls were genotyped for SNPs (n = 41) in the F2, F3 (TF), F5, F7, F10, TFPI and EPCR genes, and assayed for plasma coagulation markers (thrombin generation, activated protein C (APC) resistance, D-dimer, antithrombin, protein C, protein S, and TF pathway inhibitor (TFPI)). Associations with breast cancer were evaluated using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), or the chi-square test. Results Four SNPs in F5 (rs12120605, rs6427202, rs9332542 and rs6427199), one in F10 (rs3093261), and one in EPCR (rs2069948) were associated with breast cancer. EPCR rs2069948 was associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while the SNPs in F5 appeared to follow hormone receptor negative and triple negative patients. The prothrombotic polymorphisms factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) were not associated with breast cancer. High APC resistance was associated with breast cancer in both factor V Leiden non-carriers (OR 6.5, 95%CI 4.1-10.4) and carriers (OR 38.3, 95%CI 6.2-236.6). The thrombin parameters short lag times (OR 5.8, 95%CI 3.7-9.2), short times to peak thrombin (OR 7.1, 95%CI 4.4-11.3), and high thrombin peak (OR 6.1, 95%CI 3.9-9.5) predicted presence of breast cancer, and high D-dimer also associated with breast cancer (OR 2.0, 95%CI 1.3-3.3). Among the coagulation inhibitors, low levels of antithrombin associated with breast cancer (OR 5.7, 95%CI 3.6-9.0). The increased coagulability was not explained by the breast cancer associated SNPs, and was unaffected by ER, PR and triple negative status. Conclusions A procoagulant phenotype was found in the breast cancer patients. Novel associations with SNPs in F5, F10 and EPCR to breast cancer susceptibility were demonstrated, and the SNPs in F5 were confined to hormone receptor negative and triple negative patients. The study supports the importance of developing new therapeutic strategies targeting coagulation processes in cancer. [ABSTRACT FROM AUTHOR]

Mortality from cardiovascular disease (CVD), second tumours, and other causes is of clinical interest in the long-term follow-up of breast cancer (BC) patients. Using a cohort of BC patients (N = 6758) from the cancer registries of Girona and Tarragona (north-eastern Spain), we studied the 10-year probabilities of death due to BC, other cancers, and CVD according to stage at diagnosis and hormone receptor (HR) status. Among the non-BC causes of death (N = 720), CVD (N = 218) surpassed other cancers (N = 196). The BC cohort presented a significantly higher risk of death due to endometrial and ovarian cancers than the general population. In Stage I, HR- patients showed a 1.72-fold higher probability of all-cause death and a 6.11-fold higher probability of breast cancer death than HR+ patients. In Stages II-III, the probability of CVD death (range 3.11% to 3.86%) surpassed that of other cancers (range 0.54% to 3.11%). In Stage IV patients, the probability of death from any cancer drove the mortality risk. Promoting screening and preventive measures in BC patients are warranted, since long-term control should encompass early detection of second neoplasms, ruling out the possibility of late recurrence. In patients diagnosed in Stages II-III at an older age, surveillance for preventing late cardiotoxicity is crucial.

Background: Less than 1% of all breast cancer cases are found in men, who reportedly have inferior outcomes compared with matched women patients. Ethnic differences may also affect their prognosis. Here, we investigated overall survival (OS) and major prognostic factors for male breast cancer (MBC) in a cohort of Egyptian patients. Methods: We retrospectively analyzed OS in a cohort of 69 male patients with MBC who were surgically treated at the Mansoura Cancer Center, Egypt between 2000 and 2007. We registered demographic data, age, height, weight and body mass index, tumor size, histology, number of infiltrated axillary lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM staging. Patients' OS was the primary endpoint. Patients received treatment to the medical standards at the time of their diagnosis. Results: In the 69 patients who met the inclusion criteria and had complete stored patient data, tumors ranged from T1c to T3. We could gather cancer-related survival data from only 56 patients. The collective 5-year survival in this cohort was 46.4%. Only five patients had distant metastasis at diagnosis, but they showed a null percent 5-year survival, whereas those with no lymph node infiltration showed a 100% 5-year survival. Lymph node status and tumor grading were the only prognostic factors that significantly affected OS. Conclusions: Lymph node status and tumor grade are the most important prognostic factors for overall survival of MBC in Egyptian male patients; whereas even remarkably low HR expression in MBC did not significantly affect OS. Further research is needed to understand the factors that affect this disease. [ABSTRACT FROM AUTHOR]

Background The relationship between physical activity (PA) throughout life and the risk of postmenopausal breast cancer overall and by estrogen receptor (ER) and progesterone receptor (PR) status, has been reported, but without consistent results. The present study aimed to investigate PA from young age to adulthood in participants of the Norwegian Women and Cancer (NOWAC) Study, in order to determine whether changes in PA level affect the risk of postmenopausal breast cancer. Methods 1767 invasive breast cancer cases were identified among 80,202 postmenopausal participants of the NOWAC Study during 8.2 years of median follow-up. PA levels at age 14 years, 30 years and at cohort enrollment were obtained via a self-administered questionnaire. Multivariate Cox proportional hazard regression models were used to estimate relative risks and 95% confidence intervals of the risk of postmenopausal breast cancer overall and by ER/PR status. Results Risk of postmenopausal breast cancer overall and by ER/PR status was not associated with physical activity level at enrollment. Women with a low PA level at age 30 had an increased risk of ER+/PR + breast tumors (P for trend = 0.04) compared to women with a moderate physical activity level at age 30. Women with a low physical activity level at all three periods of life had a 20% significantly reduced risk of postmenopausal breast cancer, as well as a reduced risk of ER+/PR + and ER+/PR- breast tumors, compared with women who maintained a moderate physical activity level. However, when analyses were corrected for multiple tests, the result was no longer statistically significant. The findings were consistent over strata of age, body mass index and use of hormone replacement therapy. Conclusions The study results from this large Norwegian cohort do not support an association between physical activity at different periods of life and the risk of postmenopausal breast cancer. [ABSTRACT FROM AUTHOR]