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The absence of effective therapeutic targets and aggressive nature of triple-negative breast cancer (TNBC) renders this disease subset difficult to treat. Although estrogen receptor beta (ERβ) is expressed in TNBC, studies on its functional role have yielded inconsistent results. However, recently, our preclinical studies, along with other observations, have shown the potential therapeutic utility of ERβ in the context of mutant p53 expression. The current case study examines the efficacy of the selective estrogen receptor modulator tamoxifen in p53-mutant TNBC with brain metastases. Significant increase in ERβ protein expression and anti-proliferative interaction between mutant p53 and ERβ were observed after cessation of tamoxifen therapy, with significant regression of brain metastases. This case study provides supporting evidence for the use of tamoxifen in p53-mutant, ERβ+TNBC, especially in the setting of brain metastasis., (© The Author(s) 2023. Published by Oxford University Press.)

Breast fibroepithelial lesions (FEL) are biphasic tumors which consist of benign fibroadenomas (FAs) and the rarer phyllodes tumors (PTs). FAs and PTs have overlapping features, but have different clinical management, which makes correct core biopsy diagnosis important. This study used whole-slide images (WSIs) of 187 FA and 100 PT core biopsies, to investigate the potential role of artificial intelligence (AI) in FEL diagnosis. A total of 9228 FA patches and 6443 PT patches was generated from WSIs of the training subset, with each patch being 224 × 224 pixel in size. Our model employed a two-stage architecture comprising a convolutional neural network (CNN) component for feature extraction from the patches, and a recurrent neural network (RNN) component for whole-slide classification using activation values from the global average pooling layer in the CNN model. It achieved an overall slide-level accuracy of 87.5%, with accuracies of 80% and 95% for FA and PT slides respectively. This affirms the potential role of AI in diagnostic discrimination between FA and PT on core biopsies which may be further refined for use in routine practice., (© 2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3 . We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. The primary endpoint was rate of overall survival at 3 months (OS3). Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. Twenty patients-17 with breast cancer, two with lung cancer and one with ovarian cancer-were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia (n = 6), nausea (n = 7) and vomiting (n = 7). The study met the primary endpoint, as 12 of 20 (OS3, 0.60; 90% confidence interval, 0.39-0.78) patients were alive at 3 months after enrollment. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab.

The paradigm for post-operative cavity radiation therapy has shifted to more targeted, less morbid approaches. Single-fraction or hypofractionated radiation therapy is a common approach to treating the postoperative cavity but is associated with a local failure rate 20-40%. We employed an alternative treatment strategy involving fractionated partial brain radiation therapy to the surgical cavity. Patients with brain metastases who underwent radiation treatment 30-42 Gy in 3 Gy/fraction regimens to surgical cavity were retrospectively identified. The 6-month and 12-month freedom from local failure rates were 97.0% and 88.2%. Three patients (7%) experienced local failure at 4, 6, and 22 months. Of these, the histologies were colorectal adenocarcinoma (N = 1) and breast adenocarcinoma (N = 2). The 6-month and 12-month freedom from distant brain metastases rates were 74.1% and 68.8%, respectively, and the 6-month and 12-month overall survival rates were 84.9% and 64.3% respectively. The median overall survival was 39 months, and there were no events of late radionecrosis. Fractionated partial brain irradiation to the surgical cavity of resected brain metastases results in low rates of local failure. This strategy represents an alternative to SRS and WBRT.

The characteristics of brain metastases (BM) that develop after breast-conserving therapy (BCT) for early-stage breast cancer (BC) remain incompletely defined. We examined 1,434 consecutive patients with stage I/II invasive BC who received BCT from 1997 to 2006, 91 % of whom received adjuvant systemic therapy, according to BC subtype. Median follow-up was 85 months. Overall 5-year cumulative incidence of BM was 1.7 %; 0.1 % for luminal A, 3.3 % for luminal B, 3.2 % for luminal-HER2, 3.7 % for HER2, and 7.4 % for triple negative (TN). Women who developed BM were more likely at BC diagnosis to be younger (P < .0001) and have node-positive (P < .0001), grade 3 (P < .0001), hormone receptor-negative (P = .006), and HER2-positive (P = .01) tumors. Median time from BC diagnosis to BM was 51.4 months (range, 7.6-108 months), which was longer among luminal versus non-luminal subtypes (P = .0002; median, 61.4 vs. 34.5 months). Thirty-four percent of patients who developed distant metastases (DM) eventually developed BM. Median time from DM to BM was 12.8 months but varied by subtype, including 7.4 months for TN, 9.6 months for luminal B, and 27.1 months for HER2. Eighty-one percent of all BM patients presented with neurologic symptoms. Median number of BM at diagnosis was two, and median BM size was 15 mm, with TN (27 mm) and luminal B (16 mm) exhibiting the largest median sizes. In conclusion, the risk of BM after BCT varies significantly by subtype. Given the large size and symptomatic presentation among luminal B and TN subtypes, earlier BM detection might improve quality of life or increase eligibility for non-invasive treatments including stereotactic radiosurgery. Women with DM from these two BC subtypes have a high incidence of BM with a short latency, suggesting an ideal target population for trials evaluating the utility of MRI screening.

Purpose: The aims of this study were to determine the changes in breast and excision cavity volumes after whole-breast irradiation and the adequacy of using the surgical scar to guide boost planning., Methods and Materials: A total of 30 women consecutively treated for 31 breast cancers were included in this study. Simulation CT scans were performed before and after whole-breast irradiation. CT breast volumes were delineated using clinically defined borders. Excision cavity volumes were contoured based on surgical clips, the presence of a hematoma, and/or other surgical changes. Hypothetical electron boost plans were generated using the surgical scar with a 3-cm margin and analyzed for coverage., Results: The mean CT breast volumes were 774 and 761 cc (p = 0.22), and the excision cavity volumes were 32.1 and 25.1 cc (p < 0.0001), before and after 40 Gy (39-42 Gy) of whole-breast irradiation, respectively. The volume reduction in the excision cavity was inversely correlated with time elapsed since surgery (R = 0.46, p < 0.01) and body weight (R = 0.50, p < 0.01). The scar-guided hypothetical plans failed to cover the excision cavity adequately in 62% and 53.8% of cases using the pretreatment and postradiation CTs, respectively. Per the hypothetical plans, the minimum dose to the excision cavity was significantly lower for tumors located in the inner vs. outer quadrants (p = 0.02) and for cavities >20 cc vs. <20 cc (p = 0.01)., Conclusions: This study demonstrates a significant reduction in the volume of the excision cavity during whole-breast irradiation. Scar-guided boost plans provide inadequate coverage of the excision cavity in the majority of cases.

Background: The accurate prediction of nonsentinel node (NSN) metastasis in breast cancer patients remains uncertain., Methods: The medical records of 574 breast cancer patients from 2 different institutions (Mayo Clinic and University of Michigan) with sentinel lymph node biopsy examination and completion axillary lymph node dissection were reviewed for multiple clinicopathologic variables. The Memorial Sloan Kettering Cancer Center nomogram performance for prediction of NSN metastases was assessed. A new model was developed with clinically relevant variables and possible advantages., Results: The Memorial Sloan Kettering Cancer Center nomogram predicted the likelihood of NSN metastasis with an area under the receiver operating characteristic curve of .72 and .86. For predicted probability cut-off points of 5% and 10%, the false-negative rates were 0% and 14% (Mayo), and 17% and 11% (Michigan). A new model was developed with similar area under the curve but lower false-negative rates for low-probability subgroups., Conclusions: Predictive models for NSN tumor burden are imperfect.

Background: The use of isosulfan blue dye in sentinel node biopsy for breast cancer has been questioned because of its risk of allergic reaction. We hypothesized that blue dye could be safely omitted in the subgroup of patients who have evidence of successful sentinel node localization by lymphoscintigraphy., Methods: A retrospective review of patients with breast cancer and sentinel node biopsy was conducted. Information was collected on lymphoscintigraphy results, use of blue dye, and intraoperative and pathologic findings of sentinel nodes., Results: We identified 475 patients with breast cancer who underwent 478 sentinel node biopsies. Both dye and isotope were given in 418 cases, of which 380 had a positive lymphoscintigram. In 5 of the 380 cases with a positive lymphoscintigram, the sentinel nodes obtained were blue but not hot, for a 1.3% marginal benefit of dye in the technical success of the procedure. Sentinel nodes positive for metastasis were found in 102 of 380 cases; in 3 cases, the only positive sentinel node was blue but not hot. Omission of the blue dye tracer would have increased the false-negative rate of the sentinel node procedure by approximately 2.5%., Conclusions: Even in sentinel node biopsy cases with a positive lymphoscintigram, the use of blue dye is beneficial for both improving the technical success of the procedure and reducing the false-negative rate of the procedure. Because the marginal benefits of dye justify its routine use, strategies to minimize the toxicity of blue dye are warranted.