Adjuvant Trastuzumab in HER2-Positive Breast Cancer

Jonsson Comprehensive Cancer Center, University of California–Los Angeles, Los Angeles, CA 90095-1678, USA.
New England Journal of Medicine (Impact Factor: 55.87). 10/2011; 365(14):1273-83. DOI: 10.1056/NEJMoa0910383
Source: PubMed

ABSTRACT Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.
We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.
At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.
The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 number, NCT00021255.).

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Available from: Marc Buyse, Jan 12, 2014
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    • "For example, data from the Cancer Research Network found 5‐year combined HF/CM rates of 12.1% for patients treated with trastuzumab alone, and 20.1% for patients treated with trastuzumab and anthracyclines.(2012) The likely explanation for this difference is that clinical trials typically enrolled younger and healthier subjects, while excluding older patients or those with existing heart disease or cardiac risk factors such as uncontrolled hypertension.(2011) Because women older than 65 years comprise nearly 40% of all breast cancer patients,(2012) estimates of cardiac risk from clinical trials may not necessarily be appropriate for many patients in the general population. "
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    ABSTRACT: Adjuvant trastuzumab improves survival for women with human epidermal growth factor receptor 2-positive breast cancer, but increases risk for heart failure (HF) and cardiomyopathy (CM). However, clinical trials may underestimate HF/CM risk because they enroll younger subjects with fewer cardiac risk factors. We sought to develop a clinical risk score that identifies older women with breast cancer who are at higher risk of HF or CM after trastuzumab. Using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified women with breast cancer who received adjuvant trastuzumab. Using a split-sample design, we used a proportional hazards model to identify candidate predictors of HF/CM in a derivation cohort. A risk score was constructed using regression coefficients, and HF/CM rates were calculated in the validation cohort. The sample consisted of 1664 older women (mean age 73.6 years) with 3-year HF/CM rate of 19.1%. A risk score consisting of age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes mellitus, hypertension, and renal failure was able to classify HF/CM risk into low (0 to 3 points), medium (4 to 5 points), and high (≥6 points) risk strata with 3-year rates of 16.2%, 26.0%, and 39.5%, respectively. A 7-factor risk score was able to stratify 3-year risk of HF/CM after trastuzumab between the lowest and highest risk groups by more than 2-fold in a Medicare population. These findings will inform future research aimed at further developing a clinical risk score for HF/CM for breast cancer patients of all ages.
    Journal of the American Heart Association 12/2014; 3(1):e000472. DOI:10.1161/JAHA.113.000472 · 4.31 Impact Factor
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    • "Gene expression studies have confirmed the existence of at least four distinct and reproducible breast cancer subtypes with molecular differences based on these markers (Perou et al. 2000). These differences have resulted in stratification in the clinical setting with varying treatment algorithms based on subtype (Paik et al. 2006, Slamon et al. 2011). "
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    ABSTRACT: Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26–3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26–2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies. Electronic supplementary material The online version of this article (doi:10.1186/2193-1801-3-727) contains supplementary material, which is available to authorized users.
    SpringerPlus 12/2014; 3(1):727. DOI:10.1186/2193-1801-3-727
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    • "Only 5% of women enroll in breast cancer trials, and those women are substantially younger, have less comorbidity and higher functional status than those treated outside of trials [3]. Many trials cannot follow patients long enough to assess outcomes like congestive heart failure that can substantially impact quality of life [4] [5]. "
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    ABSTRACT: Background Growing numbers of older women receive adjuvant breast cancer therapies, but little is known about the long-term effects of current therapies upon health-related quality of life outside of clinical trials. Methods A population-based cohort of postmenopausal women with incident breast cancer aged sixty-five and older was identified from Medicare claims from four states and followed over five years. General health-related quality of life (HRQOL) was assessed using the Medical Outcomes Study SF-12 Health Survey, and breast cancer-related HRQOL was assessed using the breast cancer subscale of the functional assessment of cancer therapy (FACT-B BCS). The association of HRQOL with sociodemographic variables, comorbidity, and breast cancer variables (stage, treatments, and treatment sequelae) was examined in longitudinal models. Results Among the 3083 older breast cancer survivors, general HRQOL as measured by SF-12 mental and physical component scores was similar to norms for non-cancer populations, and remained stable throughout follow-up. Breast cancer treatments, including surgery and radiation, adjuvant hormonal therapy, and cytotoxic chemotherapy were not associated with worsened general health scores. A similar pattern was seen for breast cancer-related HRQOL scores, except that chemotherapy was associated with slightly worse scores. Lymphedema occurred in 17% of the cohort, and was strongly associated with all measures of HRQOL. Reductions in general HRQOL with lymphedema development were larger than those with an age increase of 10 years. Conclusions There is little association of breast cancer treatment with HRQOL in older breast cancer patients followed for up to five years, but the development of lymphedema is associated with substantial reductions in HRQOL.
    The Breast 10/2014; 23(5). DOI:10.1016/j.breast.2014.06.002 · 2.38 Impact Factor
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