Intestinal Microbiota Influence Doxorubicin Responsiveness in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly aggressive with a poor 5-year survival rate. Targeted therapy options are limited and most TNBC patients are treated with chemotherapy. This study aimed to determine whether doxorubicin (Dox) shifts the gut microbiome and whether gut microbiome populations influence chemotherapeutic responsiveness. Female BALB/c mice (n = 115) were injected with 4T1-luciferase cells (a murine syngeneic TNBC model) and treated with Dox and/or antibiotics, high-fat diet-derived fecal microbiota transplant (HFD-FMT), or exogenous lipopolysaccharide (LPS). Metagenomic sequencing was performed on fecal DNA samples. Mice that received Dox were stratified into Dox responders or Dox nonresponders. Mice from the Dox responders and antibiotics + Dox groups displayed reduced tumor weight and metastatic burden. Metagenomic analysis showed that Dox was associated with increased Akkermansia muciniphila proportional abundance. Moreover, Dox responders showed an elevated proportional abundance of Akkermansia muciniphila prior to Dox treatment. HFD-FMT potentiated tumor growth and decreased Dox responsiveness. Indeed, lipopolysaccharide, a structural component of Gram-negative bacteria, was increased in the plasma of Dox nonresponders and FMT + Dox mice. Treatment with exogenous LPS increases intestinal inflammation, reduces Dox responsiveness, and increases lung metastasis. Taken together, we show that modulating the gut microbiota through antibiotics, HFD-FMT, or by administering LPS influenced TNBC chemotherapy responsiveness, lung metastasis, and intestinal inflammation.

Does Localization Technique Matter for Non-palpable Breast Cancers?

BACKGROUND: There are several techniques for localization of non-palpable breast tumors, but comparisons of these techniques in terms of margin positivity and volume of tissue resected are lacking. METHODS: Between 2011-2013 and 2016-2018, 2 randomized controlled trials involving 10 centers across the United States accrued 631 patients with stage 0-3 breast cancer, all of whom underwent breast conserving surgery. Of these, 522 had residual non-palpable tumors for which localization was required. The localization technique was left to the discretion of the individual surgeon. We compared margin positivity and volume of tissue resected between various localization techniques. RESULTS: The majority of the patients (n = 465; 89.1%) had wire localization (WL), 50 (9.6%) had radioactive seed (RS) localization, and 7 (1.3%) had Savi Scout (SS) localization. On bivariate analysis, there was no difference in terms of margin positivity (37.8% vs. 28.0% vs. 28.6%, P = .339) nor re-excision rates (13.3% vs. 12.0% vs. 14.3%, P = .961) for the WL, RS, and SS groups, respectively. Further, the volume of tissue removed was not significantly different between the 3 groups (71.9 cm3 vs. 55.8 cm3 vs. 86.6 cm3 for the WL, RS, and SS groups, respectively, P = .340). On multivariate analysis, margin status was affected by tumor size (OR = 1.336; 95% CI: 1.148-1.554, P<.001) but not by type of localization (P = .670). CONCLUSIONS: While there are a number of methods for tumor localization, choice of technique does not seem to influence volume of tissue resected nor margin status.

Evaluation of the Axillary Surgery Performed in Clinically Node-Positive Breast Cancer Patients Following Neoadjuvant Chemotherapy.

BACKGROUND: The American College of Surgeons Oncology Group Z1071 trial in 2013 demonstrated the fesability of sentinel lymph node biopsy in clinically node-positive patients following neoadjuvant chemotherapy. The goal of this study was to determine the continued impact of this study on our practice pattern. MATERIALS AND METHODS: This is a retrospective review of institutional changes in the management of axillary nodal disease following the publication of Z1071. Patients with clinically node-positive disease that completed neoadjuvant chemotherapy between 2014 and 2020 were included. The Cocoran-Armitage trend test was used to analyze change in categorical variables over time, and the Spearman's rank coefficient was used to analyze two-ranked variables. RESULTS: A cohort of 102 patients were included in the study and demonstrated that the number of sentinel lymph node biopsies to evaluate axillary disease increased over time. Additionally, the number of biopsies of suspicious nodes, and the use of marker clips on the biopsied nodes increased over time. CONCLUSION: Our institution has continued to incorporate the result from Z1071 in our practice patterns.

Patients opting for breast reconstruction following mastectomy: an analysis of uptake rates and benefit.

For women with breast cancer who undergo a mastectomy, breast reconstruction offers improved psychological and cosmetic outcomes. We analyzed the rates of breast reconstruction and potential benefits to these women. The review was based on a PubMed search using the terms "reconstruction," "mastectomy," "rates," "benefits," and "breast cancer." Breast-reconstruction rates have continued to rise in recent years; however, there are definite barriers to widespread use of this procedure. These barriers include age, ethnicity, income, tumor characteristics, and the need for adjuvant radiation therapy. There are notable psychological advantages to women who receive breast reconstruction. These women also express an improved quality of life. Breast reconstruction is an acceptable technique for women undergoing mastectomy. It should be offered to all women in an immediate or delayed fashion, with guidance from their physician about the benefits and risks.