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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]

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]

Background: Data on breastfeeding and breast cancer risk are sparse and inconsistent for Hispanic women.Methods: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the United States and Mexico, we examined the association of breastfeeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, and the joint effects of breastfeeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression.Results: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER- and PR- breast cancer. Increasing duration of breastfeeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR = 0.73; 95% CI = 0.60, 0.89; Ptrend = 0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breastfeeding further reduced HR+ breast cancer risk. Additionally, breastfeeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth.Conclusions: Our findings suggest that breastfeeding is associated with reduced risk of both HR+ and ER- and PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages. [ABSTRACT FROM AUTHOR]

This viewpoint is a personal reflection on the values and merits of immunohistochemistry in current breast cancer diagnosis. Immunohistochemistry is a validated mainstay in molecular subtyping of invasive breast cancer. Immunohistochemical assessment of hormone receptor status and HER2 expression is used to determine the clinico-pathological surrogate of breast cancer intrinsic subtypes, which guide neoadjuvant and adjuvant therapy. The advent of genomic prognostic signatures and qualitative mRNA-based assays makes some clinicians and researchers wonder whether immunohistochemistry should be abandoned. However, the perils and pitfalls of these mRNA-based tests cannot be neglected. This viewpoint offers a brief overview of quality issues in immunohistochemistry and qPCR, as well as a concise summary of currently available evidence on the correlation of immunohistochemistry and mRNA-based testing for prognostic and predictive markers in invasive breast cancer. We strongly advocate the use of immunohistochemistry as it integrates valuable spatial information with quantification of protein expression. [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]

Abstract: We investigated treatment effects by oestrogen receptor (ER) status among women with metastatic breast cancer (MBC) receiving capecitabine (C) plus docetaxel (D) or D alone in a randomised phase III trial. Data were retrospectively analysed from patients whose disease had recurred following (neo)adjuvant anthracyclines. ER status was identified in 356/506 patients. In patients with ER-positive tumours, median overall survival from enrolment was 17.7 months with CD versus 12.5 months with D (hazard ratio [HR] 0.65, 95% confidence interval [CI]: 0.47–0.89; P = 0.007) and median time to progression (TTP) was 6.8 and 5.4 months, respectively (HR 0.62, 95% CI: 0.46–0.84; P = 0.002). For patients with ER-negative tumours, significantly longer TTP was seen with CD (5.2 versus 3.5 months; HR 0.73, 95% CI: 0.53–0.98; P = 0.038). Whether there is an additional C to D treatment benefit in ER-positive versus ER-negative MBC requires further evaluation. [Copyright &y& Elsevier]

Abstract: Objective: CD44+CD24−/low-expressing tumor cells have been studied as tumorigenic stem cells in vitro study. This study was designed to determine the clinical implication of the CD44 and CD24 expression in breast cancer. Methods: Tissue microarray blocks containing 643 consecutive cases of invasive breast carcinomas from 1993 to 1998 were immunostained for CD44 and CD24. The median follow-up period was 127 months. Results: CD44−CD24+ phenotype was associated with frequent hormone receptor positivity and Her2/neu positivity (P = 0.000; Both). The CD44+CD24− phenotype was inversely associated with lymph node metastasis (P = 0.002), and it showed positive associations with prolonged disease-free survival (DFS; P = 0.003) and overall survival (OS; P = 0.002). 10-year DFS and OS were 68.9% and 74.6% for CD24 negative group, 55.6% and 60.9% for CD24 positive group (P = 0.001; Both). 10-year DFS and OS were 62.2% and 68.1% for CD44 negative group, 73% and 77.7% for CD44 positive group (P = 0.012, P = 0.013, respectively). In a multivariate analysis, CD24 expression was negatively related to OS only in the receptor positive group (Hazard ratio = 2.03; P = 0.003; 95% CI: 1.27–3.24) and CD44 expression was positively related to OS only in the hormone receptor negative group (hazard ratio = 0.58; P = 0.022; 95% CI: 0.36–0.92). Conclusions: The CD44+CD24− group is considered a favorable prognostic subgroup in breast cancer. CD24 expression was a poor prognosis marker in hormone receptor positive breast cancer, and CD44 expression was a good prognostic marker in the receptor negative group. [Copyright &y& Elsevier]

Abstract: The study examines the management and outcomes of women with early invasive breast cancer treated in rural and metropolitan centres over a nine-year observation period. A prospective audit of the treatment and outcomes of 2081 women with early breast cancer who underwent potentially curative surgery between 1997 and 2006 in metropolitan Canberra or in the surrounding rural region was completed. Overall, there was good agreement between published guidelines and the treatment received by the women in the study. However, women treated in rural centres were less likely to receive postoperative radiotherapy after breast-conserving surgery, or to undergo axillary lymph node surgery or sentinel lymph node biopsy compared with women treated in metropolitan centres. Surgery in a rural centre was associated with increased breast cancer recurrence (HR = 1.54, p < 0.001) and increased breast cancer mortality (HR = 1.84, p < 0.001), after adjustment for age and tumour characteristics. Non-cancer related mortality was increased in women treated in rural centres compared with women travelling to a metropolitan centre for surgery (HR = 2.08; p = 0.005). There were differences in both the care provided and treatment outcomes between women treated in rural centres and women treated in metropolitan centres. However, the increased non-cancer related mortality in women treated in rural centres suggests an increased medical comorbidity in this group. Initiatives supporting rural-based surgeons to adopt new procedures such as sentinel node biopsy may help to optimise rural breast cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: The tailored treatment of patients with primary breast carcinoma relies mainly on the assessment of invasion, metastatic potential and responsiveness to targeted therapies. Accordingly, the role of the pathologist is to ensure the most accurate evaluation of the prognostic and predictive parameters, which will have a major impact in the planning of the adjuvant interventions. Every effort has to be made to improve the accuracy and the inter-laboratory reproducibility of the histopathological and biological characterization of breast carcinomas, taking advantage of the newly developed molecular assays. This review article will focus mainly on some controversial issues, like intracystic papillary carcinomas, whose invasive or non-invasive nature is still debated; the suitability of sophisticated molecular assays to assess the metastatic potential of primary breast carcinomas better than what is currently done; and the need for modifying the scoring criteria of the assays to assess tumor responsiveness to anti-HER2 treatments. [Copyright &y& Elsevier]