Stage IV Non-breast Cancer Patients and Screening Mammography: It is Time to Stop.

BACKGROUND: Patients diagnosed with metastatic cancer have shortened life expectancy with questionable benefit of routine screening mammography (SM). The aim of this study was to evaluate the incidence and consequences of continued SM in the setting of reduced survival from stage IV non-breast cancer. METHODS: Women diagnosed with Stage IV non-breast cancer at a single institution from 2015 to 2019 were queried from the institutional tumor registry for demographics, stage IV cancer diagnosis, and survival. Incidence and timing of SM after stage IV diagnosis and further diagnostic workup were extracted from the medical record. RESULTS: 790 women with Stage IV non-breast cancer were identified, 109 (14%) had at least 1 SM, 23% required diagnostic mammography, 7% breast biopsy, and 1% breast surgery. No breast cancers were identified. SM was ordered most often in stage IV gynecological cancers (28%), with more common cancers still seeing a high percentage of patients screened (lung 10%, colorectal 15%). Study 3-year survival was 26% (95% confidence interval [CI] 23-30%), with 74% mortality during follow up and median time from Stage IV diagnosis to death of 1.2 years (CI 0.4-2.3 years). Of patients screened, 41/109 died within 2 years of undergoing SM. CONCLUSIONS: Despite low overall survival for patients diagnosed with metastatic non-breast cancer, 14% of women underwent SM which resulted in additional imaging, biopsies, and surgery with no new breast cancers identified. Continued SM in this population offers risk without benefit of reduced breast cancer mortality and should no longer continue in women with stage IV non-breast cancer.

Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer.

PURPOSE: Despite extensive genomic and transcriptomic profiling, it remains unknown how signaling pathways are differentially activated and how tumors are differentially sensitized to certain perturbations. Here, we aim to characterize AKT signaling activity and its association with other genomic or IHC-based PI3K/AKT pathway biomarkers as well as the clinical activity of ipatasertib (AKT inhibitor) in the FAIRLANE trial. EXPERIMENTAL DESIGN: In FAIRLANE, 151 patients with early triple-negative breast cancer (TNBC) were randomized 1:1 to receive paclitaxel with ipatasertib or placebo for 12 weeks prior to surgery. Adding ipatasertib did not increase pathologic complete response rate and numerically improved overall response rate by MRI. We used reverse-phase protein microarrays (RPPA) to examine the total level and/or phosphorylation states of over 100 proteins in various signaling or cell processes including PI3K/AKT and mTOR signaling. One hundred and twenty-five baseline and 127 on-treatment samples were evaluable by RPPA, with 110 paired samples at both time points. RESULTS: Tumors with genomic/protein alterations in PIK3CA/AKT1/PTEN were associated with higher levels of AKT phosphorylation. In addition, phosphorylated AKT (pAKT) levels exhibited a significant association with enriched clinical benefit of ipatasertib, and identified patients who received benefit in the absence of PIK3CA/AKT1/PTEN alterations. Ipatasertib treatment led to a downregulation of AKT/mTORC1 signaling, which was more pronounced among the tumors with PIK3CA/AKT1/PTEN alterations or among the responders to the treatment. CONCLUSIONS: We showed that the high baseline pAKT levels are associated with the alterations of PI3K/AKT pathway components and enriched benefit of ipatasertib in TNBC.

The effect of wound complications following mastectomy with immediate reconstruction on breast cancer recurrence.

INTRODUCTION: The aim of this study was to determine whether complications following mastectomy with immediate breast reconstruction (IBR) were associated with breast cancer recurrence. METHODS: A retrospective review was performed of women diagnosed with stage I-III breast cancer who underwent mastectomy with IBR between 2005 and 2010. Patient demographics, tumor data, surgical wound complications, treatment details and timing were recorded and analyzed. RESULTS: We identified 458 women with a median follow up time of 7.6 years. A total of 22% of patients experienced IBR complications. There was a delay in initiation of adjuvant therapy in patients who had a complication (52 vs 41 days, p < 0.001). There was no significant difference in recurrences between groups with and without complications (p = 0.65). CONCLUSIONS: In breast cancer patients who undergo mastectomy with IBR, wound complications delayed initiation of adjuvant systemic therapy, but were not associated with an increased risk of cancer recurrence.