Oncologic safety of axillary lymph node dissection with immediate lymphatic reconstruction.

PURPOSE: Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) can reduce the incidence of lymphedema in patients with breast cancer. The oncologic safety of ILR is unknown and has not been reported. The purpose of this study was to evaluate if ILR is associated with increased breast cancer recurrence rates. METHODS: Patients with breast cancer who underwent ALND with ILR from September 2016 to December 2020 were identified from a prospective institutional database. Patient demographics, tumor characteristics, and operative details were recorded. Follow-up included the development of local recurrence as well as distant metastasis. Oncologic outcomes were analyzed. RESULTS: A total of 137 patients underwent ALND with ILR. At cancer presentation, 122 patients (89%) had clinically node positive primary breast cancer, 10 patients (7.3%) had recurrent breast cancer involving the axillary lymph nodes, 3 patients (2.2%) had recurrent breast cancer involving both the breast and axillary nodes, and 2 patients (1.5%) presented with axillary disease/occult breast cancer. For surgical management, 103 patients (75.2%) underwent a mastectomy, 22 patients (16%) underwent lumpectomy and 12 patients (8.8%) had axillary surgery only. The ALND procedure, yielded a median of 15 lymph nodes pathologically identified (range 3-41). At a median follow-up of 32.9 months (range 6-63 months), 17 patients (12.4%) developed a local (n = 1) or distant recurrence (n = 16), however, no axillary recurrences were identified. CONCLUSION: Immediate lymphatic reconstruction in patients with breast cancer undergoing ALND is not associated with short term axillary recurrence and appears oncologically safe.

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.

Time to Completion of Breast Cancer Treatment and Survival.

BACKGROUND: Breast cancer treatment delays are common. This study was designed to examine the association between the time interval from time of diagnosis to completion of all acute breast cancer treatment modalities (surgery, chemotherapy, and radiation therapy) and survival. METHODS: A retrospective analysis was performed utilizing data from the National Cancer Database (NCDB) to determine an association between the duration of time from diagnosis to completing all acute breast cancer treatment (surgery, chemotherapy, and radiation therapy) and survival. Secondary survival analysis evaluated whether delay in treatment completion varied by differences in tumor receptor status. RESULTS: We analyzed 2010 NCDB data of stage I-III breast cancer patients. A subset of 28,284 patients received all three modalities (surgery, chemotherapy, and radiation) as their acute treatment. Median follow-up was 5.8 years. Cox proportional hazards model identified a cut-off showing the risk of delaying completion of all treatment beyond 38 weeks was associated with a decrease in overall survival (hazard ratio [HR] 1.21). This decrease in survival was significant regardless of the major tumor receptor status: triple-negative (HR 1.188, 95% confidence interval [CI] 1.06-1.34), estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)- (HR 1.22, 95% CI 1.09-1.36), ER-/PR-/HER2+ (HR 1.29, 95% CI 1.004-1.67), and ER+/PR+/HER2+ (HR 1.32, 95% CI 1.01-1.72). CONCLUSION: Efforts to improve the efficiency of multimodality breast cancer treatment and reduce treatment delays should be a priority to optimize breast cancer patient outcomes.

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.

Radiographically guided shave margins may reduce lumpectomy re-excision rates.

Minimizing margin re-excision optimizes patient care by providing appropriate oncologic resection and reducing costs. This study aims to assess margin positivity rate in two groups: shave margin based on gross specimen (control group, CG) vs shave margin based on intraoperative imaging (radiographic group, RG). A total of 182 patients who underwent lumpectomy for stage O-III breast cancer at a single institution from January 2013 to January 2014 were evaluated. There was statistically significant decrease in margin re-excision rate with intraoperative mammography but not with ultrasound. Surgeons are ideally equipped to use intraoperative imaging to guide margin excision, thus, improving care and reducing costs.

Do Primary Care Physician Perform Clinical Breast Exams Prior to Ordering a Mammogram?

Both the American Cancer Society and National Comprehensive Cancer Network recommend annual clinical breast examination (CBE) along with screening mammogram (SM) for patients starting at 40 years of age. However, patients with a palpable breast mass should have a diagnostic mammogram (DM) during workup. Review at our institution demonstrated that 11% of patients with newly diagnosed breast cancer and self-identified breast mass had SM instead of DM. This led us to question whether primary care physicians (PCP) perform CBE prior to ordering mammography. As part of the routine preimaging screening, patients were asked if they had undergone breast examination by a medical provider prior to mammogram order. Data on mammogram type, ordering physician specialty, and presence of symptoms on day of mammogram were recorded. Of 6,109 mammograms, 4,823 were ordered by PCPs. CBE was performed prior to 67.2% SM and 64.8% DM (p = 0.12). OB/GYN performed statistically significantly higher CBE (81.6%) compared to internal (45.4%) and family (50.5%) medicine physicians (p < 0.001). Of patients with self-reported breast symptoms, 8.7% had SM ordered rather than DM. Despite recommendations, approximately 1/3 of women report not having CBE prior to mammogram. The chances of having a CBE varied significantly by PCP specialty. Lack of CBE can lead to incorrect type of mammogram, with possibly increased cost and delay in diagnosis. Further evaluation is needed to understand why CBE was not performed in some patients.