Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients.

BACKGROUND: ESR1 mutation has recently emerged as one of the important mechanisms involved in endocrine resistance. The incidence and clinical implication of ESR1 mutation has not been well evaluated in heavily pretreated breast cancer patients. METHODS: We conducted a retrospective review of advanced breast cancer patients with tumors who underwent next-generation sequencing genomic profiling using Foundation One test at Cancer Treatment Centers of America(®) regional hospitals between November 2012 and November 2014. RESULTS: We identified a total of 341 patients including 217 (59%) estrogen receptor (ER)+, 177 (48%) progesterone receptor (PR)+, 30 (8%) hormone receptor+/HER2 positive, and 119 (32%) triple negative patients. ESR1 mutation was noted in 27/222 (12.1%) ER+ or PR+ breast cancer patients. All ER+ patients received at least one line of an aromatase inhibitor. All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). In this cohort, 19 (67.9%) patients carried three or more, seven (25%) patients had one or two additional genomic alterations and one (3.6%) patient had an ESR1 mutation only. Of 28 patients, three patients were treated with fulvestrant immediately before and two patients were treated after next-generation sequencing testing; only one patient achieved stable disease for 8 months and the other four patients had progression of disease. In all, 3/3 (100%) patients before testing and 2/4 (50%) after testing treated with exemestane and everolimus achieved stable disease for at least 6 months. CONCLUSION: ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.

Management of two cases of recurrent anal carcinoma.

Due to the low incidence of anal cancer and generally high cure rates, few second-line treatment options have been evaluated in the setting of formal clinical trials. We briefly report two cases that were both found to have wild-type K-RAS, with no epidermal growth factor receptor amplification or evidence of prior persistent human papilloma virus infection. Both cases were treated with irinotecan and cetuximab with evidence of clinical benefit in the setting of a third recurrence, as well as evidence of response to other strategies employed in their management. These cases provide support for the suggestion that treatment planning in conjunction with molecular profiling may be beneficial in such uncommon clinical settings.

Clinically meaningful responses to sequential gemcitabine-based chemotherapy regimens in a patient with metastatic pancreatic cancer.

Pancreatic cancer exhibits profound chemoresistance resulting either from pre-existing (intrinsic) mechanisms, or from anticancer drug treatment itself (acquired chemoresistance). We present the case of a patient with pancreatic adenocarcinoma metastatic to the liver who experienced clinical, radiographic and tumor marker response to three lines of gemcitabine-based chemotherapy. The regimens included: 8 cycles of gemcitabine and oxaliplatin (GEMOX), 8 cycles of gemcitabine, docetaxel and capecitabine (GTX) and more than 3 cycles of gemcitabine and nab-paclitaxel, with an exceptional response 2 years from the initiation of chemotherapy for metastatic pancreatic cancer.

Synchronous presentation of a primary iliac lymph node plasmacytoma and a prostate adenocarcinoma.

Synchronous presentation of primary nodal plasmacytoma and prostate cancer is very rare and has not been described in the literature. Here, we report a case of a patient with nodal plasmacytoma whose clinical presentation was suggestive of metastatic prostate cancer in the setting of recently diagnosed prostate cancer. The workup and treatment of both malignancies as well as a possible underlying common pathologic mechanism (IL-6 gene mutation) are discussed.

Blood type, hormone receptor status, HER2/neu status, and survival in breast cancer: a retrospective study exploring relationships in a phenotypically well-defined cohort.

PURPOSE: Altered glycosylation has been associated with oncogenic potential. Relationships of blood types (where expression is due to glycosylation pattern) and HER2/neu (where expression arises due to altered glycosylation) and breast cancer-associated markers like estrogen receptor/progesterone receptor (ER/PR) were examined and related to outcomes in patients with breast cancer. METHODS: A population-based retrospective study of 426 surgical breast cancer patients examined relationships between (1) patient characteristics, (2) breast tumor characteristics, and (3) outcomes of women diagnosed at the same medical center over a 10-year period relative to specific molecules defined by glycosylation patterns (eg. blood group, HER2/neu) and (4) ER/PR status. RESULTS: Following stratification by blood group, subjects exhibited significant differences in tumor size with persons in blood groups A and B having greater numbers of tumors ≤ 2 cm and those with blood types AB and O having tumors >2 cm. After adjusting for age, disease stage, and treatment with trastuzumab, tamoxifen, or aromatase inhibitors, no significant differences were observed in 5-year overall and disease-free survival based on blood type grouping. Blood group B was over-represented among the breast cancer cohort compared to the reference population, while blood group AB was under-represented. CONCLUSION: No significant differences were observed in overall and disease-free survival based on blood group. No correlation was noted between HER2/neu, ER or PR status, and blood group type. Among this cohort, HER2/neu positivity was less than 20% and correlated with a 5-year disease-free survival rate ≥ 75% and overall survival of >80% across all blood groups.