Berry, D. A. et al. Estrogen-Receptor Status and Outcomes of Modern Chemotherapy for Patients With Node-Positive Breast Cancer. JAMA 295, 1658-1667

University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 05/2006; 295(14):1658-67. DOI: 10.1001/jama.295.14.1658
Source: PubMed


Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy.
To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors.
Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment.
Disease-free and overall survival.
For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%.
Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.

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    • "Chemotherapies and radiation therapy induce DNA damage, so ERα may suppress the DDR to reduce the efficacy of these treatments. Indeed, patients with ER positive breast cancers have significantly lower response rates to chemotherapy than those with ER negative cancers (88), and in vitro studies suggest this is dependent on ERα action (89–91). Co-administration of anti-estrogens and radiation therapy or chemotherapy appears to enhance therapy cytotoxicity and a likely explanation is that anti-estrogen treatment prevents pro-proliferative bypass of cytotoxicity by estrogen (66, 90). "
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    ABSTRACT: Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR) and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1, and p53 and the feedback on estrogen receptor signaling from these proteins. We put forward the hypothesis that estrogen receptor signaling converges to suppress effective DNA repair and apoptosis in favor of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer, which will further change the processing of DNA damage. Finally, the action of estrogen signaling on DNA damage is also relevant to the therapeutic setting as the suppression of a DDR by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.
    Frontiers in Oncology 05/2014; 4:106. DOI:10.3389/fonc.2014.00106
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    • "Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment, and its determination has become a standard practice in the management of breast carcinomas [3]. "
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    ABSTRACT: Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.
    PLoS ONE 02/2014; 9(2):e89172. DOI:10.1371/journal.pone.0089172 · 3.23 Impact Factor
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    • "In related to HR status and systemic therapy, accumulating evidence suggests that the effect of conventional chemotherapy is greater among HR-negative breast cancers (Berry et al. 2006). This is particular striking in the neoadjuvant setting; HR-negative breast cancer is more likely to achieve a pCR to NAC compared to those with HR-positive breast cancer (Ring et al. 2004). "
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    ABSTRACT: We report a case of synchronous locally advanced bilateral breast cancer with different pathological responses to neoadjuvant chemotherapy with different biological character. The patient had presented bilateral breast cancer: the left breast cancer was hormone receptor negative, human epidermal growth factor receptor-2 (HER2) positive, and classified as T4bN1M0, stage IIIb, while the right was hormone receptor positive, HER2-negative, and classified as T4bN0M0, stage IIIb. We administered four cycles of anthracycline-based therapy followed by 12 weekly cycles of taxane with trastuzumab for neoadjuvant chemotherapy. We had achieved a significant left tumor reduction after each chemotherapy, but not right tumor. Bilateral modified radical mastectomies with axillary lymph-node dissection were performed. The therapeutic effect in the left was determined as a pathological complete response, in contrast to the right side. She has no recurrence for more than five years, though she had advanced cancer with oncologic emergency. This case could be an informative experience to understand the relation of tumor biology and response to systemic therapy.
    SpringerPlus 12/2013; 2(1):272. DOI:10.1186/2193-1801-2-272
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