Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis

Introduction Breast cancer at a young age is associated with an unfavorable prognosis. Very young patients with breast cancer therefore are advised to undergo adjuvant chemotherapy irrespective of tumor stage or grade. However, chemotherapy alone may not be adequate in young patients with hormone receptor-positive breast cancer. Therefore, we studied the effect of adjuvant chemotherapy in young patients with breast cancer in relation to hormone receptor status. Methods Paraffin-embedded tumor material was collected from 480 early-stage breast cancer patients younger than 41 years who participated in one of four European Organization for Research and Treatment of Cancer trials. Using immunohistochemistry on the whole series of tumors, we assessed estrogen receptor (ER) status and progesterone receptor (PgR) status in a standardized way. Endpoints in this study were overall survival (OS) and distant metastasis-free survival (DMFS). The median follow-up period was 7.3 years. Results Overall, patients with ER-positive tumors had better OS rates (hazard ratio [HR] 0.63; P = 0.02) compared with those with ER-negative tumors. However, in the subgroup of patients who received chemotherapy, no significant difference in OS (HR 0.87; P = 0.63) and DMFS (HR 1.36; P = 0.23) was found between patients with ER-positive tumors or those with ER-negative tumors. These differences were similar for PgR status. Conclusion Young patients with hormone receptor-positive tumors benefit less from adjuvant systemic chemotherapy than patients with hormone receptor-negative tumors. These results confirm that chemotherapy alone cannot be considered optimal adjuvant systemic treatment in breast cancer patients 40 years old or younger with hormone receptor-positive tumors

Targeted therapy for breast cancer prevention.

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer

Associations of Premenopausal Hysterectomy and Oophorectomy With Breast Cancer Among Black and White Women: The Carolina Breast Cancer Study, 1993–2001

Black women experience higher rates of hysterectomy than other women in the United States. Although research indicates that premenopausal hysterectomy with bilateral oophorectomy decreases the risk of breast cancer in black women, it remains unclear how hysterectomy without ovary removal affects risk, whether menopausal hormone therapy use attenuates inverse associations, and whether associations vary by cancer subtype. In the population-based, case-control Carolina Breast Cancer Study of invasive breast cancer in 1,391 black (725 cases, 666 controls) and 1,727 white (939 cases, 788 controls) women in North Carolina (1993–2001), we investigated the associations of premenopausal hysterectomy and oophorectomy with breast cancer risk. Compared with no history of premenopausal surgery, bilateral oophorectomy and hysterectomy without oophorectomy were associated with lower odds of breast cancer (for bilateral oophorectomy, multivariable-adjusted odds ratios = 0.60, 95% confidence interval: 0.47, 0.77; for hysterectomy without oophorectomy, multivariable-adjusted odds ratios = 0.68, 95% confidence interval: 0.55, 0.84). Estimates did not vary by race and were similar for hormone receptor–positive and hormone receptor–negative cancers. Use of estrogen-only menopausal hormone therapy did not attenuate the associations. Premenopausal hysterectomy, even without ovary removal, may reduce the long-term risk of hormone receptor–positive and hormone receptor–negative breast cancers. Varying rates of hysterectomy are a potentially important contributor to differences in breast cancer incidence among racial/ethnic groups

Evaluation of a Novel Anti-Mucin 1 (MUC1) Antibody (PankoMab) as a Potential Diagnostic Tool in Human Ductal Breast Cancer; Comparison with Two Established Antibodies

Aim: PankoMab is a novel antibody that recognizes a tumor-specific epitope of Mucin 1 (MUC1). The aim of this study was the evaluation of PankoMab as a potential diagnostic tool and its comparison with two established antibodies against MUC1 in human ductal breast cancer. Materials and Methods: Breast carcinomas were obtained from 82 patients. MUC1 expression and hormone receptor status were determined by immunohistochemistry of paraffin-embedded material. Results: PankoMab revealed strong correlation to hormone receptor expression. DF3 showed no correlation with grading, lymph node involvement and/or estrogen receptor (ER) expression. In the subgroup of lymph node-positive and ER-negative tumors, we saw a significantly reduced DF3 staining in G3 tumors compared to G2 tumors. VU-4-H5 showed increased staining intensity in correlation with increased grading. In addition, we also identified a significantly higher expression of the VU-4-H5 epitope in lymph node-positive carcinomas compared to carcinomas without lymph node involvement. Conclusion: PankoMab revealed strong correlation to hormone receptor expression in ductal carcinoma of the breast. VU-4-H5 showed increased staining intensity in correlation with increased grading and lymph node involvement. PankoMab and VU-4-H5 staining could be a useful combination in ductal breast cancer prognosis by immunohistochemistry

Molecular heterogeneity in breast carcinoma cells with increased invasive capacities

Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes. Materials and methods. In order to reach this aim, parental and invasive (INV) MDA-MB-231 (triple-negative), T47D (hormone receptor-positive), and Au565 (Her2-positive) breast carcinoma cells were used and their molecular phenotypes were compared using a proteomic approach. Results. Independently from breast cancer subtypes, INV cells have demonstrated fibroblast-like morphology accompanied by enhancement of invasive and migratory capacities, increased expression of cancer stem cell markers, and delayed tumor growth in in vivo animal models. However, the global proteomic analysis has highlighted that INV cells were different in protein expressions from the parental cells, and Her2-positive Au565-INV cells showed the most pronounced molecular differences compared to the triple-negative MDA-MB-231-INV and hormone receptor-positive T47D-INV cells. Although Au565-INV breast carcinoma cells possessed the highest number of deregulated proteins, they had the lowest overlapping in proteins commonly expressed in MDA-MB-231-INV and T47D-INV cells. Conclusions. We can conclude that hormone receptor-positive cells with increased invasiveness acquire the molecular characteristics of triple-negative breast cancer cells, whereas Her2-positive INV cells specifically changed their own molecular phenotype with very limited partaking in the involved pathways found in the MDA-MB-231-INV and T47D-INV cells. Since hormone receptor-positive invasive cells share their molecular properties with triple-negative breast cancer cells, we assume that these types of metastatic disease can be treated rather equally with an option to add anti-hormonal agents. In contrast, Her2-positive metastasis should be carefully evaluated for more effective therapeutic approaches which are distinct from the triple-negative and hormone-positive metastatic breast cancers

Adjuvant chemotherapy and survival among patients 70 years of age and younger with node-negative breast cancer and the 21-gene recurrence score of 26-30

BACKGROUND: The benefits of chemotherapy in node-negative, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with the 21-gene recurrence score (RS) of 18-30, particularly those with RS 26-30, are not known. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) data, we retrospectively identified 29,137 breast cancer patients with the 21-gene RS of 18-30 diagnosed between 2004 and 2015. Mortality risks according to the RS and chemotherapy use were compared by the Kaplan-Meier method and Cox\u27s proportional hazards model. RESULTS: Among the breast cancer patients with the RS 18-30, 21% of them had RS 26-30. Compared to breast cancer patients with RS 18-25, patients with RS 26-30 had more aggressive tumor characteristics and chemotherapy use and increased risk of breast cancer-specific mortality and overall mortality. In breast cancer patients who were aged ≤ 70 years and had RS of 26-30, chemotherapy administration was associated with a 32% lower risk of breast cancer-specific mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.47-0.99) and a 42% lower risk of overall mortality (HR, 0.58; 95% CI, 0.44-0.76). Survival benefits were most pronounced in breast cancer patients who were younger or had grade III tumor. CONCLUSIONS: The 21-gene RS of 18-30 showed heterogeneous outcomes, and the RS 26-30 was a significant prognostic factor for an increased risk of mortality. Adjuvant chemotherapy could improve the survival of node-negative, hormone receptor-positive, and HER2-negative breast cancer patients with the 21-gene RS 26-30 and should be considered for patients, especially younger patients or patients with high-grade tumors

CA 15.3 measurements for separating FDG PET/CT positive from negative findings in breast carcinoma recurrence

In breast cancer CA 15.3 is considered the tumour marker of choice. CA 15.3 is directly related to the disease extent and to hormone status (estrogen receptor ER+/ ER-, progesterone receptor PR+/PR-). This study was designed to assess the impact of disease extent, hormone receptor and HER2-status, and circulating blood volume on the area-under the ROC-curve of CA 15.3 to separate FDG PET positive from negative findings. Patients, methods: We retrospectively evaluated 379 FDG PET/CT examinations performed in 80 patients with breast cancer. Blood volumes were derived using the formulas by Nadler and multiplied by their corresponding CA 15.3 measurement. Results: ROC-curve analysis revealed an AUC of 0.695 (p = 0.0001) for CA 15.3 to separate FDG PET positive from negative findings. AUC measurements to separate normal scan findings from loco-regional disease and metastatic disease were 0.527 (p = 0.587) and 0.732 (p = 0.0001), respectively. AUC measurements for CA 15.3 to separate positive from negative FDG PET findings, in ER+ and ER-patients, were respectively 0.772 (p = 0.0001) and 0.596 (p = 0.143). AUC measurements for CA 15.3 to separate positive from negative FDG PET findings, in PR+ and PR-patients, were respectively 0.675 (p = 0.0001) and 0.694 (p = 0.0001). In HER2-positive and -negative patients, the AUC measurements were respectively 0.594 (p = 0.178) and 0.701 (p = 0.0001) to separate positive from negative FDG PET findings. Conclusion: The AUC for CA 15.3 measurements to separate FDG PET positive from negative findings in breast cancer patients with suspected recurrence proved to be directly related to the extent of the recurrent disease and hormone receptor status and inversely related to HER2-status. Correcting CA 15.3 measurements for blood volumes did not impact the AUC

Controversies in adjuvant endocrine therapy for pre- and post-menopausal women with breast cancer

AbstractNearly 80% of breast cancer are hormone receptor positive. The efficacy of hormonal adjuvant therapy of breast cancer was expressed in the most recent EBCTG overview analysis of randomised trials using adjuvant tamoxifen. Five years of adjuvant tamoxifen led to proportional risk reduction, in terms of recurrence and mortality for hormone receptor positive patients, of 47% and 26%, respectively. This benefit was constant, regardless of menopausal status, age or whether or not chemotherapy was administered. More recent trials evaluating the use of aromatase inhibitors have challenged the standard of hormonal therapy in post-menopausal patients. However, many questions have been raised from these trials: (a) the optimal management of patients with hormone receptor positive breast cancer in terms of selection of hormonal agents and its sequence and duration; (b) the role of ovarian suppression in pre-menopausal patients; and (c) the actual role of biomolecular markers in clinical decision

Family History and Breast Cancer Hormone Receptor Status in a Spanish Cohort

Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women.A population-based study was conducted in the city of Santiago de Compostela, Spain. A total of 645 women diagnosed with operable invasive breast cancer between 1992 and 2005 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics of the tumors were collected. Hormone receptor negative tumors were compared with hormone receptor postive tumors on their clinico-pathological characteristics as well as risk factor profiles.Among the 645 breast cancer patients, 78% were estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+), and 22% were ER−&PR−. Women with a family history of breast cancer were more likely to have ER−&PR− tumors than women without a family history (Odds ratio, 1.43; 95% confidence interval, 0.91–2.26). This association was limited to cancers diagnosed before age 50 (Odds ratio, 2.79; 95% confidence interval, 1.34–5.81).An increased proportion of ER−&PR− breast cancer was observed among younger Spanish women with a family history of the disease

Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Background: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. Methods: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer. Results: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (+/- 2.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% confidence interval 1.22-1.65] in ever HRT users (HR = 1.23; 1.04-1.44), in never HRT users (HR = 1.40; 1.16-1.68) and in oestrogen-and-progesterone-receptor-positive (ERthornPRthorn) breast cancer (HR = 1.46; 1.15-1.85). Conclusion: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer