Remarkable response to combined immunochemotherapy in patients with metastatic triple-negative breast cancer.

Background: Progress in immunotherapy (IT) has shifted treatment paradigms for multiple malignancies. In March 2019, the combination of nab-paclitaxel and atezolizumab was approved by the US FDA for patients with PD-L1 positive metastatic triple-negative breast cancer based on positive results of the Impassion130 trial. Although numerous studies have examined the prognostic role of PD-L1, the value of this test remains controversial. Results: Here, we presented the cases of three heavily pretreated women with metastatic triple-negative breast cancer who exhibited remarkable responses to combined IT and chemotherapy despite undetectable PD-L1. Conclusion: In our opinion, the current FDA-approved assessment for PD-L1 expression is a reasonable tool for deciding whether to start IT. However, because this approach has many limitations, patients with undetectable PD-L1 expression should still be considered for IT.

Atypical Presentation of Radiation-Associated Breast Angiosarcoma: A Case Report and Review of Literature.

BACKGROUND Radiation-associated breast angiosarcoma is a rare clinical entity that is thought to be increasing in incidence. CASE REPORT Here we present the case of a 67-year-old female with a history of left breast invasive ductal carcinoma who received breast conserving surgery and radiation therapy eight years ago. She then presented with a painless mild skin discoloration of the left breast that had been present for over one year. Mammograms and ultrasounds were normal. A punch biopsy and a subsequent excisional biopsy revealed the diagnosis of angiosarcoma. The patient was treated with mastectomy and had no subsequent recurrences. CONCLUSIONS The long-term clinical surveillance for all patients who receive breast conservation surgery is recommended and a high degree of suspicion should be exercised in view of potential atypical presentations of this disease.

Use of non-selective ß-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

Previous studies suggest beta-adrenergic receptor (ß-AR) antagonists (ß-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of ß1-AR and ß3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of ß-blocker usage on tumor proliferation. Our analysis revealed that non-selective ß-blockers, but not selective ß-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of ß-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective ß-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3ß. In conclusion, use of non-selective ß-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

Surgical Decision Making in the BRCA-Positive Population: Institutional Experience and Comparison with Recent Literature.

A retrospective study was performed to document the uptake and extent of surgical intervention in patients with a known mutation in the BRCA1/2 genes and associated outcomes. Data were collected retrospectively on BRCA-positive patients with and without cancer at the time of genetic testing. Our findings were compared to those published in the current literature. Of patients with cancer at testing, 61% chose bilateral mastectomies. Of patients without cancer, 54% chose risk-reducing surgery (RRS) including risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), or both. Time to surgery was significantly shorter to RRSO than to RRM. The literature suggests and our data support that acceptance of RRM in the BRCA-positive population has gradually increased over time. Consistently high rates of RRSO uptake and short intervals from time-of-testing to RRSO demonstrate that RRSO is still more acceptable to this population than RRM.

Breast cancer detection in axillary sentinel lymph nodes: the impact of the method of pathologic examination.

At Carolinas Medical Center, before 2008, axillary sentinel lymph nodes (SLNs) from breast cancer patients were evaluated with a single hematoxylin and eosin-stained slide. In 2008, the protocol changed to include a limited step sectioning at 500 µm. In this study, we compared the intraoperative and permanent section pathologic findings for SLN biopsies from 2006 to 2007 to those from 2009 to 2010. We hypothesized that evaluating 2 slides would increase the detection of micrometastases and isolated tumor cells (ITCs) on permanent sections and correspondingly decrease the sensitivity of intraoperative touch preparation cytology (IOTPC). From 2006 to 2007, 140 (23.5%) of 597 of SLN permanent sections contained tumor cells: 92 macrometastases (65.7%), 36 micrometastases (25.7%), and 12 ITCs 0.2 mm or less (8.6%). The sensitivity of IOTPC for 2006 to 2007 was 51.4% for any tumor cells and 71.7% for macrometastases. From 2009 to 2010, 160 (21.9%) of 730 SLN permanent sections were positive for any tumor cells: 76 macrometastases (47.5%), 55 micrometastases (34.4%), and 29 ITCs (18.1%). The sensitivity of IOTPC for 2009 to 2010 was 39.4% for any tumor cells and 76.3% for macrometastases. With limited step sectioning, we observed an approximately 10% increase in the detection of both micrometastases and ITCs in SLN. The increased detection of ITCs on permanent sections reached statistical significance (P = .018). However, under current clinical guidelines, patients with limited SLN involvement may not be required to undergo completion axillary lymph node dissection. The ability to detect SLN tumor deposits less than 2 mm must be balanced with the clinical utility of doing so.

Morbidity and mortality among patients with hip fractures surgically repaired within and after 48 hours.

OBJECTIVE: The objectives were (1) to compare the morbidity and mortality of patients with hip fractures surgically repaired within and after 48 hours of the occurrence of fracture and (2) to establish whether timing of repair alone had a major role in determining how the patients fared after the surgical repair or whether comorbidities also affected outcomes. SAMPLE: The study involved the medical records of 49 patients (aged 51 to 99 years) admitted to Coney Island Hospital between January 2003 and January 2004 with a primary diagnosis of hip fracture who underwent surgical repair. DESIGN: Analysis of data was done by retrospective chart review of patients admitted with the diagnosis of hip fracture to an acute care hospital setting. Follow-up continued until the patients were transferred to a rehabilitation facility for physical or occupational therapy after surgery. OUTCOME MEASURES: The preoperative health status of each patient was assessed by cardiopulmonary risk index score, based on comorbid conditions, and postoperative outcome was determined by complications (such as bed sores, pneumonia, urinary tract infection, deep vein thrombosis, or pulmonary embolism) or death. RESULTS: Patients who underwent early surgical repair (within 48 hours) had fewer postoperative complications (14.7%, as compared with 33.3% in the group undergoing surgery >48 hours after fracture). CPRI scores in the early and delayed surgery groups were also compared with regard to postoperative mortality and morbidity. It appeared that there was a higher statistical correlation between CPRI scores and complications among patients in the early surgery group (P=0.39) and an insignificant correlation among patients in the delayed surgery group (P=0.07). CONCLUSION: Surgical repair of hip fractures within the first 48 hours was associated with better health outcomes in a nationally representative sample, as observed in an acute care facility, irrespective of comorbid conditions.