Purpose: In estrogen receptor–positive (ER+)/HER2− breast cancer, multiple measures of intratumor heterogeneity are associated with a worse response to endocrine therapy. We sought to develop a novel experimental model to measure heterogeneity in response to tamoxifen treatment in primary breast tumors. Experimental Design: To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live normal breast specimens and human tumors immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses. Live primary cell suspensions were treated ex vivo with tamoxifen (10 µmol/L) or control media for 12 hours, and single-cell RNA libraries were generated using the 10X Genomics droplet-based kit. Results: In total, we obtained and processed normal breast tissue from two women undergoing reduction mammoplasty and tumor tissue from 10 women with ER+/HER2− invasive breast carcinoma. We demonstrate differences in tamoxifen response by cell type and identify distinctly responsive and resistant subpopulations within the malignant cell compartment of human tumors. Tamoxifen resistance signatures from resistant subpopulations predict poor outcomes in two large cohorts of ER+ breast cancer patients and are enriched in endocrine therapy–resistant tumors. Conclusions: This novel ex vivo model system now provides the foundation to define responsive and resistant subpopulations within heterogeneous human tumors, which can be used to develop precise single cell–based predictors of response to therapy and to identify genes and pathways driving therapeutic resistance.

Papillary tumors of the pineal region (PTPR) can be observed among adults with poor prognosis and high recurrence rates. Standards of therapy involve total surgical excision along with radiation therapy, with no promising prospects for primary adjuvant chemotherapy, as long-term treatment options have not been explored. Chromosome 10 loss is characteristic of PTPR, and PTEN gene alterations are frequently encountered in a wide range of human cancers and may be treated with mTORC1 inhibitors such as everolimus. In parallel, there are no reports of treating PTPR with everolimus alone as a monopharmacotherapy. We report the case of a patient diagnosed with PTPR (grade III) characterized by a PTEN R130Q alteration with chromosome 10 loss that was treated with everolimus pharmacotherapy alone, resulting in an asymptomatic course and tumor regression, a rare yet notable phenomenon not described in the literature so far with potential to alter the management approach to patients with PTPR.

Jenny H. Chang, Rasha T. Kakati, Chase Wehrle, Robert Naples, Daniel Joyce, Toms Augustin, Robert Simon, R Matthew Walsh, Fadi S. Dahdaleh, Philip Spanheimer, Isabella Salti, Alessandro Parente, Samer A. Naffouje. Journal of Minimally Invasive Surgery 2024;27:95-108. https://doi.org/10.7602/jmis.2024.27.2.95

By the time they complete breast cancer therapy, many young patients are still of childbearing age. We aim to estimate the incidence of pregnancies in women who completed treatment and examine the percentage of patients who received fertility counseling before initiation of therapy. Electronic health records of breast cancer patients between 2008 and 2014 at AUBMC were screened for exclusion criteria of having metastatic disease or known infertility, still receiving therapy, and being above 42 years at diagnosis. Data about therapy and tumor characteristics was obtained for the included survivors who were interviewed as well via telephone for information about fertility preservation counseling, pregnancy occurrence, and delivery. 451 breast cancer patients were identified. 39 patients remained after application of exclusion criteria. 30.76% (n = 12) wanted more children at the time of diagnosis. 10.25% (n = 4) of all 39 patients treated for breast cancer achieved one or more pregnancy after a median time of 3.83 years after completion of therapy. 25% (n = 3) of women who wanted more children at diagnosis (n = 12) were able to conceive. 23.07% (n = 9) of patients discussed fertility with their primary oncologist prior to treatment initiation. 35.89% (n = 14) of patients were aware of fertility preservation technique availability, but none of these patients used one. The observed rate of pregnancy is comparable to the literature. There is a lack in fertility counseling of breast cancer patients, and the rate of use of fertility preservation techniques is very low despite prior knowledge about their availability.

Immunotherapy poses new considerations and alterations to the management of metastatic colorectal carcinoma (mCRC), where chemotherapy achieves complete radiological response but yields complete pathological response in few patients only. Immunotherapy may be superior in the conversion of unresectable disease to resectable liver lesions from mCRC and downsizing borderline lesions for more feasible resectability and achieving complete pathologic response, with the potential for cure and to alter current, established guidelines for surgical resection with a shift from chemotherapy. We present two patients with hepatic lesions from mCRC characterized by deficient mismatch repair (dMMR) which were unresectable after traditional chemotherapy but were converted to resectable lesions with a complete histopathological response following immunotherapy. Complete histopathologic response and radiologic regression or disappearance of liver lesions was observed in patients with dMMR mCRC after pembrolizumab. Immunotherapy exhibits notable potential for cure, achieving complete, successful surgical resection and improving prognosis.

Injuries of the biliary tract and complex injuries involving vascular and parenchymal tissue can be detrimental despite the improved use of laparoscopy. Complex biliary injuries are variable depending on the type of injury as well as patient and surgeon factors. We present four cases of complex biliary injuries at our tertiary referral center with hepatobiliary expertise: biliary stenosis with obstruction, double duct system anatomy, combined right hepatic arterial transection and biliary duct injury, and a complete pedicle injury. Early identification and specialized repair of complex biliary injuries is essential to minimize patient morbidity. Notably, consulting a specialist intraoperatively in case of difficult dissection and visualization or a suspected injury and considering bail-out strategies such as a subtotal cholecystectomy or conversion are safe approaches to minimize complex biliary injuries. Earlier recognition and repair of complex biliary injuries improves outcomes when immediate intraoperative repair can be performed rather than delayed postoperatively.