Pembrolizumab in Patients With Metastatic Breast Cancer With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

PURPOSE: The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported. METHODS: Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks. Simon's two-stage design was used with a primary study end point of disease control (DC) defined as objective response or stable disease of at least 16 weeks duration. If two or more patients in stage I achieved DC, the cohort would enroll 18 additional patients in stage II. Secondary end points include progression-free survival (PFS), overall survival, and safety. RESULTS: Twenty-eight patients were enrolled from October 2016 to July 2018. All patients' tumors had HTMB ranging from 9 to 37 mutations/megabase. DC and objective response were noted in 37% (95% CI, 21 to 50) and 21% of patients (95% CI, 8 to 41), respectively. Median PFS was 10.6 weeks (95% CI, 7.7 to 21.1); median overall survival was 30.6 weeks (95% CI, 18.3 to 103.3). No relationship was observed between PFS and tumor mutational burden. Five patients experienced ≥ 1 serious adverse event or grade 3 adverse event at least possibly related to pembrolizumab consistent with the product label. CONCLUSION: Pembrolizumab monotherapy has antitumor activity in heavily pretreated patients with mBC characterized by HTMB. Our findings support the recent US Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with HTMB without alternative treatment options.

Male patient with metastatic stage IV breast cancer achieves complete remission on second line Abemaciclib, Fulvestrant and Leuprolide: A case report.

Male breast cancer occurs rarely, comprising <1% of breast cancers. Due to the low incidence of male breast cancer, clinical trials of this disease are lacking. Therefore, therapeutic strategies utilized in the management of female breast cancer are often applied to male patients with breast cancer. Specifically, clinical outcomes using CDK 4/6 inhibitors require further investigation in male patients. To the best of our knowledge, the present report presents the first known case of a male patient treated with second line Abemaciclib, Lupron and Fulvestrant, producing complete remission. To the best of our knowledge this is also the first report of complete remission in a male breast cancer patient with a regimen utilizing a CDK 4/6 inhibitor.

Smoking and survival in male breast cancer patients.

The purpose of the article was to assess whether smoking affects survival in male breast cancer patients for the overall population and when stratified by race, ethnicity, and socioeconomic status. Data were obtained by linking the 1996-2007 Florida Cancer Data System, the Florida Agency for Health Care Administration, and the US Census. Inclusion criteria were males ≥18 years, diagnosed with breast cancer and residing in Florida (n = 1573). To analyze the association between smoking and survival, we performed sequential multivariate Cox proportional hazards regression models with progressive adjustment for main confounders. Compared to never smokers, worse survival was found in current (hazard ratio = 1.63; 95 % CI = 1.23-2.16) but not in former smokers (1.26; 0.99-1.59). Those who smoked ≥1 packs/day had worse survival (2.48; 1.59-3.87) than never smokers with a significant dose-response (P for linear trend <0.001). Race-ethnic stratified models comparing current and former smokers with never smokers found significant differences among Whites [(1.88; 1.44-2.44) and (1.31; 1.04-1.65, respectively)] and non-Hispanics, [(1.73; 1.31-2.28) and (1.31; 1.04-1.66, respectively)]. Overall, current smokers were found to have significantly reduced survival, which was worse by intensity of smoking. Also, any smoking history is associated with worse survival in White and non-Hispanic male breast cancer patients compared to never smokers. Thus, male breast cancer patients should be advised to quit smoking.

Smoking and survival in female breast cancer patients.

The purpose of this study was to determine if smoking affects survival in female breast cancer patients, both overall and stratified by race, ethnicity, and socioeconomic status. We linked data from the 1996-2007 Florida cancer data system, the Florida Agency for Health Care Administration, and the U.S. census. Inclusion criteria were females ≥18 years, diagnosed with breast cancer, and residing in Florida (n = 127,754). To analyze the association between smoking and survival, we performed sequential multivariate Cox proportional hazard regression models with progressive adjustment for main confounders. Compared to never smokers, worse survival was found in current (hazard ratio 1.33; 95 % CI 1.28-1.38) and former smokers (1.09; 1.06-1.13). Those who smoked <1, 1-2, and >2 packs/day had worse survival (HR 1.28; 1.20-1.36; HR 1.40; 1.33-1.47 and 1.70; 1.45-1.99, respectively) (p for linear trend <0.001), than never smokers. Among Whites, current and former smokers had worse survival (HR 1.38; 1.33-1.44 and HR 1.11; 1.07-1.15, respectively) than never smokers. Worse survival was also found for current and former smokers (HR 1.34; 1.29-1.40 and HR 1.10; 1.06-1.15, respectively) compared with never smokers among non-Hispanics; similarly, worse survival was found among current Hispanic smokers (HR 1.13; 1.01-1.26). The association was not significant for Blacks. Current smoking is associated with worse survival in White breast cancer patients and through all socioeconomic status categories and ethnicities compared to never smoking. Former smoking is associated with worse survival in White and non-Hispanic females. Blacks had similar survival regardless of smoking status. Nonetheless, all female breast cancer patients should be advised to quit smoking.

Oral and extraoral plasmablastic lymphoma: similarities and differences in clinicopathologic characteristics.

Plasmablastic lymphoma (PBL), initially characterized as an aggressive lymphoma arising in the jaw and oral mucosa in HIV-infected patients, was recently reported to occur with extraoral manifestations, heterogeneous histologic findings, and variable association with immunodeficiency states. We reviewed clinical, morphologic, and immunophenotypic features of 13 cases of PBL to determine whether these different subtypes represent distinct morphologic and clinical entities. Two distinct subtypes of PBL were identified and classified as oral and extraoral PBL. The oral PBLs were strongly associated with HIV infection and commonly demonstrated plasmablastic morphologic features without plasmacytic differentiation. Extraoral PBLs tended to occur in patients with underlying non-HIV-related immunosuppression and universally demonstrated plasmacytic differentiation. The patients with oral PBL demonstrated better overall survival compared with patients with extraoral PBL (P = .02). Our findings suggest that PBL with oral and extraoral manifestation represent 2 distinct clinicopathologic entities.