Breast cancer treatment is multidisciplinary. Most women with early stage breast cancer are candidates for breast-conserving surgery with radiotherapy or mastectomy. The risk of local recurrence and the chance of survival does not differ with these approaches. Sentinel node biopsy is used for axillary staging, and individualized approaches are minimizing the need for axillary dissection in women with positive sentinel nodes. Adjuvant systemic therapy is used in most women based on proven survival benefit, and molecular profiling to individualize treatment based on risk is now a clinical reality for patients with hormone receptor-positive cancers.

Patients with neoadjuvant chemotherapy to surgery intervals of up to 8 weeks had equivalent OS, RFS, and LRFS.

BackgroundVariations in single nucleotide polymorphisms (SNPs) have been associated with enhanced drug efficacy and toxicity in cancer therapy. SNP variations in the ErbB2 gene have been identified that alter the protein sequence of the HER2-neu protein, but how these polymorphisms affect prognosis and response to HER2 targeted therapy is unknown. We examined eleven ErbB2 SNPs that alter the HER2-neu amino acid sequence to determine whether any of these particular polymorphisms were associated with increased trastuzumab cardiotoxicity in a case–control study.Methods140 subjects were enrolled from a single institution under Weill Cornell Medical College IRB protocol #0804009734. Patients were eligible if they had histologically or cytologically proven HER2-neu positive breast cancer and more than 3 months of trastuzumab therapy. Cases had either symptomatic CHF or a decline in LVEF of 15% (or if the LVEF <55%, a decline in LVEF of 10%) that resulted in at least temporary discontinuation of trastuzumab, whereas controls had no decline in their LVEF. Eleven ErbB2 single gene SNPs that resulted in an alteration in the HER2-neu protein amino acid sequence were studied. Single gene SNP analysis was carried out using SNP genotyping assays from genomic DNA obtained from peripheral blood or buccal swab.ResultsOnly two of the ErbB2 SNPs (Ile 655 Val and Pro 1170 Ala) were found to have variation. There was no association between codon 665 and cardiotoxicity; however the proline variant of amino acid 1170 was more likely than the alanine variant to be found in cases with trastuzumab cardiotoxicity (35% of case patients as compared to 17% of controls, p = 0.04). This association remained significant in multivariable analysis taking into account age, race, and history of hypertension (adjusted OR = 2.60, 95% CI = 1.02, 6.62, p = 0.046).ConclusionsThe Her2/neu Pro 1170 Ala polymorphism can be used to identify a subset of patients who are at increased risk of cardiotoxicity from trastuzumab therapy. Her2/neu single nucleotide polymorphisms may be useful in conjunction with other biomarkers to risk stratify patients in order to optimize clinical management.

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Purpose 2015 NCCN guidelines recommend genetic counseling and germline BRCA mutation testing be offered to women under age 60 with triple negative breast cancer (TNBC). As a result of the 2010 ASCO/CAP guidelines in breast cancer, patients with breast cancers that are ER or PR low-positive (1–9% on immunohistochemistry) are no longer strictly considered to have TNBC and may not be referred for genetic counseling. However, the incidence of BRCA mutation in patients with hormone receptor (HR) low-positive breast cancers remains unknown, and current ASCO/CAP guidelines may result in under-testing for BRCA mutation. Methods We reviewed a prospectively maintained research database of breast cancer patients evaluated at UT MD Anderson Cancer Center between 2004 and 2014, identifying 314 patients with ER<10%, PR<10%, HER-2 neu negative breast cancers with known BRCA mutation status. Results 314 patients had breast cancers expressing ER and PR <10%; 238 (75.8%) had HR negative (ER and PR <1%) cancers and 76 (24.2%) had HR low-positive (ER and/or PR 1–9%) cancers. Among patients with HR negative tumors, 86 of 238 (36.1%) had a BRCA 1/2 mutation, while among the HR low-positive group, 30 of 76 (39.5%) had a BRCA 1/2 mutation. In multivariate analysis, HR status (HR<1% vs. HR 1–9%) was not significantly associated with BRCA 1/2 mutation. Conclusion The incidence of BRCA 1/2 mutation is similar in patients with HR low-positive and HR negative breast cancers. We recommend offering genetic counseling and BRCA testing to patients under age 60 with ER low-positive breast cancers.

Therapeutics; and grants from Kite/Gilead outside the submitted work. D. Schaer was an employee of Eli Lilly and Company at the time of the study. J. Kauh is a former employee of Eli Lilly and Company. S.F. Slovin has nothing to declare. M. Adamow has nothing to declare. V.S. Blinder reports personal fees from Pfizer outside the submitted work. M. Brahmachary is a former employee of Eli Lilly and Company and may have Eli Lilly and Company stock. M. Carlsen is an employee of Eli Lilly and Company. E. Comen reports consultancy fees from Pfizer, Novartis, Bristol Myers Squibb, COTA, Genentech-Roche, outside the scope of the submitted work. D.C. Danila reports research support from

Aims The most appropriate timing of exercise therapy to improve cardiorespiratory fitness (CRF) among patients initiating chemotherapy is not known. The effects of exercise therapy administered during, following, or during and following chemotherapy were examined in patients with breast cancer. Methods and results Using a parallel-group randomized trial design, 158 inactive women with breast cancer initiating (neo)adjuvant chemotherapy were allocated to receive (1:1 ratio): usual care or one of three exercise regimens—concurrent (during chemotherapy only), sequential (after chemotherapy only), or concurrent and sequential (continuous) (n = 39/40 per group). Exercise consisted of treadmill walking three sessions/week, 20–50 min at 55%–100% of peak oxygen consumption (VO2peak) for ≈16 (concurrent, sequential) or ≈32 (continuous) consecutive weeks. VO2peak was evaluated at baseline (pre-treatment), immediately post-chemotherapy, and ≈16 weeks after chemotherapy. In intention-to-treat analysis, there was no difference in the primary endpoint of VO2peak change between concurrent exercise and usual care during chemotherapy vs. VO2peak change between sequential exercise and usual care after chemotherapy [overall difference, −0.88 mL O2·kg−1·min−1; 95% confidence interval (CI): −3.36, 1.59, P = 0.48]. In secondary analysis, continuous exercise, approximately equal to twice the length of the other regimens, was well-tolerated and the only strategy associated with significant improvements in VO2peak from baseline to post-intervention (1.74 mL O2·kg−1·min−1, P &lt; 0.001). Conclusion There was no statistical difference in CRF improvement between concurrent vs. sequential exercise therapy relative to usual care in women with primary breast cancer. The promising tolerability and CRF benefit of ≈32 weeks of continuous exercise therapy warrant further evaluation in larger trials.

2 Background: The 2011 ASCO/CAP guidelines recommend that breast cancers with estrogen receptor (ER) staining as low as 1% on immunohistochemistry be considered ER-positive. In practice, there remains significant variability in what clinicians consider ER-positive versus ER-negative. Current NCCN guidelines recommend that patients under age 60 with triple-negative breast cancer (TNBC) be referred for genetic counseling and consideration of germline BRCA mutation testing. With the 2011 ASCO/CAP guidelines, the definition of TNBC has changed to exclude patients with ER low-positive (1-9%) tumors; hence patients with ER-low positive tumors (formerly considered ER negative) may not be referred for genetic counseling and BRCA testing. This may lead to “undertesting” of appropriate patients. The incidence of BRCA germline mutations in patients with ER-low positive versus ER-negative (0%) tumors is unknown. We sought to identify whether the incidence of BRCA mutation differed between patients with ER-negative/PR-negative/HER-2 neu negative tumors and patients with ER-low positive/PR-negative/HER-2 neu negative tumors. Methods: We performed a review of a prospectively maintained research database of all patients with ER < 10%, PR 0% and HER-2 neu–negative breast cancers who were referred for genetic risk assessment and testing for BRCA mutation at UT MD Anderson Cancer Center. Results: Of 144 patients who underwent BRCA mutation testing, 22 (15%) had ER-low positive tumors while 122 (85%) had ER-negative tumors. Among patients with ER-low positive tumors, 7 of 22 (31.8%) were found to have a deleterious BRCA 1/2 mutation, while 33 of 122 (27%) with ER-negative tumors were found to have a deleterious BRCA 1/2 mutation. The incidence of deleterious BRCA 1/2 mutation in patients with ER-low positive tumors versus those with ER-negative tumors was not statistically significantly different (p = 0.6457). Conclusions: The rate of deleterious BRCA 1/2 germline mutations in ER-negative versus ER-low positive (1-9%) breast cancer is similar. Therefore, we strongly recommend that BRCA testing continue to be offered to women under age 60 with tumors that are ER-low positive/PR-negative/HER-2 neu negative.