Neoadjuvant Endocrine Therapy for Locally Advanced Breast Cancer

Neoadjuvant Endocrine Therapy for Locally Advanced Breast Cancer

ANNOTATED BIBLIOGRAPHY Acute Chemotherapy–Related Toxicity Is Not Increased in BRCA1 and BRCA2 Mutation Carriers Treated for Breast Cancer in the Unit...

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ANNOTATED BIBLIOGRAPHY Acute Chemotherapy–Related Toxicity Is Not Increased in BRCA1 and BRCA2 Mutation Carriers Treated for Breast Cancer in the United Kingdom

Surgeons Oncology Group Z1031 trial, which is being led by the senior author of the current paper. L. A. Carey, MD

Shanley S, McReynolds K, Ardern-Jones A, et al

Reference

Clin Cancer Res 12:7025-7032, 2006 This study compared chemotherapy-associated gastrointestinal and mucosal toxicities (as recalled by the subjects) and hematologic toxicity in women with BRCA-associated breast cancer with those experienced by presumed sporadic controls. Cases and controls were, unfortunately, not well matched in several areas, and relying on recall of subjective toxicity, such as nausea, was problematic. There was no evidence of increased toxicity in BRCA1/2 mutation carriers. The power to identify differences was limited by a small sample size. Despite its limitations, the report does not support the hypothesis of increased sensitivity to DNA damage in BRCAhaploinsufficient cells, and it certainly does not indicate that BRCA1/2-mutation carriers should receive less intensive chemotherapy than other women because of fears of increased toxicity. M. E. Robson, MD

Neoadjuvant Endocrine Therapy for Locally Advanced Breast Cancer Ma CX, Ellis MJ Semin Oncol 33:650-656, 2006 This paper is a nicely written and comprehensive review of neoadjuvant endocrine therapy. As they have done with chemotherapy and novel agents, breast cancer researchers are increasingly using the neoadjuvant approach to identify optimal regimens and predictors of response. Some resistance to the neoadjuvant approach derives from its lower response and higher progression rates than are usually seen in chemotherapy trials. This resistance is unfortunate, because existing data suggest that the inferior response rates are more likely due to the nature of the tumor than the nature of the treatment. It is simply unrealistic to expect pathologic complete response (pCR) in these tumors regardless of the drug; pCR is an end point established for cytotoxic drugs in highly proliferative tumors, and it clearly does not carry the same relevance in hormone receptorpositive tumors treated with endocrine therapy. The authors discussed other intermediate biomarkers, such as Ki67, but clearly these biomarkers are works in progress. The potential contribution of hormone receptor and HER2 expression to a differential response to aromatase inhibitors versus a differential response to tamoxifen was explored extensively in the current study; however, given recent negative data presented at the San Antonio Breast Cancer Symposium from the Arimidex, Tamoxifen, Alone or in Combination trial,1 using progesterone receptor or HER2 as determinants of aromatase inhibition versus tamoxifen upfront use, which always seemed too easy, probably is. Fortunately, a comprehensive analysis of predictive markers for aromatase inhibitor response will come from studies like the American College of

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Breast Diseases: A Year Book Quarterly Vol 18 No 3 2007

1. Dowsett M, Allred DC, on behalf of the TransATAC Investigators: Relationship between quantitative ER and PgR expression and HER2 status with recurrence in the ATAC trial. Presented at the 29th Annual San Antonio Breast Cancer Symposium. Available at http://www.sabcs.org. Accessed July 25, 2007.

Prognostic Significance of Human Epidermal Growth Factor Receptor Positivity for the Development of Brain Metastasis After Newly Diagnosed Breast Cancer Gabos Z, Sinha R, Hanson J, et al J Clin Oncol 24:5658-5663, 2006 In this very relevant and timely study, Gabos and colleagues analyzed a cohort of 301 women with newly diagnosed 301 HER2–positive breast cancer and 363 with HER-2–negative breast cancer to compare the incidence of brain metastases between the 2 groups. With a median follow-up time of 3.9 years, 9% (n = 27) of patients with HER-2–overexpressing breast cancers developed brain metastases compared with only 1.9% (n = 7) of patients with HER2–negative cancers (hazard ratio 4.23; confidence interval 1.849.74; P = 0.0007). In addition to HER-2 overexpression, tumor size larger than 2 cm and hormone receptor negativity were independent prognostic factors for the development of brain metastases on multivariate analysis. Numerous papers have documented the high percentage of trastuzumab-treated patients in whom brain metastases develop during the course of treatment for metastatic disease, but this study is the first of its kind to confirm that HER-2–overexpressing breast cancer has a greater propensity for metastasis to the brain than HER-2–negative disease, even early after diagnosis. In this study, the 5-year overall survival rate was 87% for HER-2–negative patients versus 73% for HER-2–positive patients (P < 0.001), again demonstrating the more aggressive nature of HER-2–overexpressing breast cancers. Although data from the joint analysis of the National Surgical Adjuvant Breast and Bowel Project and the North Central Cancer Treatment Group adjuvant trastuzumab trials suggest that outcomes should improve significantly in the upcoming years for newly diagnosed patients with HER-2–positive disease, it is not yet clear how trastuzumab will affect the development of brain metastases. Only a small number (7.9%) of the HER-2– positive patients in this study received trastuzumab, because it was not approved in the adjuvant setting during this time period. Only 1 (3.3%) of these 30 patients developed brain metastases, suggesting that reduction in recurrence of systemic metastases with trastuzumab may have some affect on the incidence, timing, or both of recurrence in the central nervous system. Ultimately, however, imple-