Comparison of nodal metastasis between BRCA mutation carriers and non-BRCA mutation carriers with breast cancer.

OBJECTIVE: This study evaluates whether nodal status differs between breast cancer patients with BRCA mutations and those confirmed not to harbor mutations. METHODS: A prospective database identified patients with breast cancer who underwent genetic testing and axillary staging. Comparative variables included age, as well as tumor characteristics such as size, grade, lymphovascular invasion (LVI), estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2-neu), and nodal status. RESULTS: Overall, 235 patients with breast cancer underwent genetic testing for BRCA mutations from June 2000 to May 2012. Of these patients, 74 (31.4 %) were found to express BRCA 1 and/or 2 mutations, and 161 (68.5 %) patients were verified to have no detectable BRCA mutation. Among the entire 235 patients tested, 92 (39.1 %) were found to have nodal disease. In univariable analysis, only LVI and tumor size correlated with presence of nodal metastasis. Of the 74 BRCA mutation carriers, 34 (45.9 %) had nodal metastasis compared with 58 of the 161 (36 %; p = 0.15) patients without a BRCA mutation. BRCA mutation carriers with nodal disease were more likely to have poorly differentiated tumors than those without mutations who had nodal disease (24/33 [72.7 %] vs. 27/57 [47.4 %]; p = 0.027). CONCLUSION: BRCA mutations are not themselves predictive of nodal metastasis. Patients with BRCA mutations did not have a statistically significant higher prevalence of nodal metastasis than those without mutations.

Resistance to receptor-blocking therapies primes tumors as targets for HER3-homing nanobiologics.

Resistance to anti-tumor therapeutics is an important clinical problem. Tumor-targeted therapies currently used in the clinic are derived from antibodies or small molecules that mitigate growth factor activity. These have improved therapeutic efficacy and safety compared to traditional treatment modalities but resistance arises in the majority of clinical cases. Targeting such resistance could improve tumor abatement and patient survival. A growing number of such tumors are characterized by prominent expression of the human epidermal growth factor receptor 3 (HER3) on the cell surface. This study presents a "Trojan-Horse" approach to combating these tumors by using a receptor-targeted biocarrier that exploits the HER3 cell surface protein as a portal to sneak therapeutics into tumor cells by mimicking an essential ligand. The biocarrier used here combines several functions within a single fusion protein for mediating targeted cell penetration and non-covalent self-assembly with therapeutic cargo, forming HER3-homing nanobiologics. Importantly, we demonstrate here that these nanobiologics are therapeutically effective in several scenarios of resistance to clinically approved targeted inhibitors of the human EGF receptor family. We also show that such inhibitors heighten efficacy of our nanobiologics on naïve tumors by augmenting HER3 expression. This approach takes advantage of a current clinical problem (i.e. resistance to growth factor inhibition) and uses it to make tumors more susceptible to HER3 nanobiologic treatment. Moreover, we demonstrate a novel approach in addressing drug resistance by taking inhibitors against which resistance arises and re-introducing these as adjuvants, sensitizing tumors to the HER3 nanobiologics described here.

Comparison of outcomes of breast conserving therapy in multifocal and unifocal invasive breast cancer.

BACKGROUND: There is controversy about whether breast conserving therapy (BCT) should be contraindicated in multifocal (MF) breast cancer. Few studies have reported on the oncologic safety of BCT in MF breast cancer. STUDY DESIGN: We reviewed a prospective database of 1,169 women with invasive breast cancer who were treated with segmentectomy and whole breast irradiation from 1991 through 2009 and followed at our institution. Multifocal breast cancer was defined as 2 or more distinct tumors excised with a single incision or segmentectomy. We compared 2 groups, MF and unifocal breast cancer patients, with respect to demographics, tumor characteristics, adjuvant systemic therapy, local recurrence (LR), disease-free survival (DFS), and overall survival (OS). RESULTS: One hundred sixty-four patients with MF and 999 with unifocal invasive breast cancer were treated with BCT. Median follow-up was 112 months. Compared with the unifocal group, patients in the MF group had higher 10-year LR (0.6% vs 6.1%, p < 0.001) and lower 10-year DFS (97.7% vs 89.3%, p < 0.001) and OS (98.4% vs 85.8%, p < 0.001). On multivariable analysis, multifocality was independently significantly associated with local recurrence-free survival (LRFS), DFS, and OS. CONCLUSIONS: Our data suggest that BCT in MF breast cancer is oncologically safe but may result in a slightly inferior outcome compared with BCT in unifocal breast cancer.