Refining breast cancer prognosis by incorporating age at diagnosis into clinical prognostic staging: introduction of a novel online calculator.

PURPOSE: American Joint Committee on Cancer (AJCC) clinical staging is used to estimate breast cancer prognosis, but individual patient survival within each stage varies considerably by age at diagnosis. We hypothesized that the addition of age at diagnosis to the staging schema will enable more refined risk stratification. METHODS: We performed a retrospective population analysis of adult women diagnosed with invasive breast cancer between 2010 and 2015 registered in SEER. Multivariable Cox hazards models were used to evaluate the association of AJCC 8th edition clinical prognostic stage (CPS) and age with risk of overall mortality. Separate hierarchical models were fit to the data: Model 1: CPS alone; Model 2: CPS + age + age2; and Model 3: CPS + age + age2 + CPS x age + CPS x age2. Models were compared by the Akaike information criterion (AIC), the c-statistic for time-dependent receiver operator characteristic curves, and category-free net reclassification improvement (NRI). Internal validation was performed using bootstrapping samples. RESULTS: Among 86,637 women, the median follow-up was 36 months and 3-year overall survival was 91.9% ± 0.1%. Age significantly modified the effect of CPS on survival (p < 0.0001). Model 3 was the most precise, with the lowest AIC (126,619.63), the highest c-statistic (0.8212, standard error 0.0187), and superior NRI indices. CONCLUSION: Age at diagnosis is a highly prognostic variable that warrants consideration for inclusion in future editions of the AJCC Breast Cancer Staging Manual.

The effect of local therapy on breast cancer-specific mortality of women with occult breast cancer and advanced nodal disease (N2/N3): a population analysis.

PURPOSE: Current NCCN guidelines for occult breast cancer (OBC) recommend modified radical mastectomy, with the option for breast preservation with radiation instead of mastectomy for N1 patients. Our aim was to compare the effect of local therapy-mastectomy versus breast radiation-on breast cancer-specific mortality (BCSM) in a contemporary cohort of OBC patients of all nodal stages. METHODS: Competing risk analyses were performed to evaluate the effect of local therapy, nodal stage, and other demographic and clinical prognostic variables on risk of BCSM for women registered in the SEER database with T0N+M0 breast cancer from 2004 to 2015. RESULTS: Of the 353 women with OBC who underwent axillary nodal dissection, 152 received breast radiation and 201 underwent mastectomy. Overall, 57.5% had N1 disease, 54.4% had estrogen receptor (ER) positive tumors, 80.7% were white, and 88.1% received chemotherapy. Women treated with radiation were older (p < 0.001). The two groups were comparable with respect to all other variables analyzed. During a median follow-up of 66 months, 32 women died from breast cancer (radiation: 11, mastectomy: 21). Five-year cumulative incidence of BCSM was 8.0% ± 2.6% with radiation versus 10.9% ± 2.6% with mastectomy (p = 0.309). On multivariate analysis, independent predictors of BCSM included older age, higher N stage, and ER negativity, but the type of local therapy was not significantly associated with outcome. CONCLUSIONS: These results suggest that breast preservation is a reasonable alternative to mastectomy for OBC patients, regardless of nodal stage.

Quantifying the relationship between age at diagnosis and breast cancer-specific mortality.

PURPOSE: The relationship between age at diagnosis and breast cancer-specific mortality (BCSM) is unclear. The aim of this study was to examine the nature of this relationship using rigorous statistical methodology. METHODS: A historical cohort study of adult women with invasive breast cancer in the SEER database from 2000 to 2015 was conducted. Multivariable Cox's cause-specific hazards model was used to evaluate the association of age at diagnosis with risk of BCSM. Functional relationship of age was assessed using cumulative sums of Martingale residuals and the Kolmogorov-type supremum test. RESULTS: A total of 206,332 women were eligible for study. Mean age at diagnosis was 59.7 ± 13.8 years. Median follow-up was 80 months. During the study period, 21,771 women (10.6%) died from breast cancer and 18,566 (9.0%) died from other causes. Cumulative incidence of BCSM at 120 months post-diagnosis was 14.4% (95% CI 14.2-14.6%). Age was found to be quadratically related to the risk of BCSM (p < 0.001), with a nadir at 45 years of age. The final Cox model suggests that a 30-year-old woman has approximately the same adjusted BCSM risk (HR 1.187, 95% CI 1.187-1.188) as a 60-year-old woman (HR 1.174, 95% CI 1.174-1.175). CONCLUSIONS: Women diagnosed with breast cancer at the extremes of age suffer disproportionate rates of cancer-specific mortality. The relationship between age at diagnosis and adjusted risk of BCSM is complex, consistent with a quadratic function. With the growing appreciation for breast cancer as a heterogeneous disease, it is essential to accurately address age as a prognostic risk factor in predictive models.

Post-Treatment Symptoms of Pain, Anxiety, Sleep Disturbance, and Fatigue in Breast Cancer Survivors.

BACKGROUND: In part because of improvements in early detection and treatment, the number of breast cancer survivors is increasing. After treatment, however, breast cancer survivors often experience distressing symptoms, including pain, sleep disturbance, anxiety, and fatigue; at the same time, they have less frequent contact with health care providers. Pain commonly co-occurs with other symptoms and the combination of symptoms contribute to the amount of distress experienced by survivors. Previous studies of post-treatment symptoms include primarily urban and white women. AIMS: The purpose of this study was to describe the post-treatment cluster of symptoms, to examine the correlations among these symptoms, and to examine the role pain intensity may play in understanding the variation in sleep disturbance, fatigue, and anxiety in a racially diverse sample of rural breast cancer survivors. DESIGN: The theoretical framework for this descriptive correlational study was the theory of unpleasant symptoms. SETTINGS: Outpatient university-affiliated cancer clinic. PARTICIPANTS/SUBJECTS: Forty women who were between 6 months and 5 years post breast cancer diagnosis. METHODS: Participants completed the following self-report instruments: Patient Reported Outcomes Measurement Information System of pain intensity, pain interference, anxiety, and sleep disturbance and the Piper Fatigue Short Form 12. RESULTS: The average age of participants was 58 years, and 57.5% were black. Most women reported sleep disturbance (78%), pain interference (68%), and pain intensity (63%) above the national average for an American adult. Black women reported higher pain intensity than whites. There were moderate to strong correlations among the symptoms (range r = 0.35-0.89). CONCLUSIONS: Nurses and health care providers in primary care settings need to screen for symptoms, and nursing interventions are needed to assist breast cancer survivors to manage distressing symptoms.

An Evaluation of a Rural Community-Based Breast Education and Navigation Program: Highlights and Lessons Learned.

Cancer has become the leading cause of death in North Carolina (NC) (North Carolina DHHS, State Center for Health Statistics 2015) and the eastern region of North Carolina (ENC) has experienced greater cancer mortality than the remainder of the state. The Pitt County Breast Wellness Initiative-Education (PCBWI-E) provides culturally tailored breast cancer education and navigation to screening services for uninsured/underinsured women in Pitt and Edgecombe Counties in ENC. PCBWI-E created a network of 23 lay breast health educators, and has educated 735 women on breast health and breast cancer screening guidelines. Navigation services have been provided to 365 women, of which 299 were given breast health assessments, 193 were recommended for a mammogram, and 138 were screened. We have identified five lessons learned to share in the successful implementation of a community-based breast cancer screening intervention: (1) community partnerships are critical for successful community-based cancer screening interventions; (2) assuring access to free or low-cost screening and appropriate follow-up should precede interventions to promote increased use of breast cancer screening; (3) the reduction of system-based barriers is effective in increasing cancer screening; (4) culturally tailored interventions can overcome barriers to screening for diverse racial/ethnic and socioeconomic groups; and (5) multi-component interventions that include multiple community health strategies are effective in increasing screening.

Primary tumor resection in metastatic breast cancer: A propensity-matched analysis, 1988-2011 SEER data base.

Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score-matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score-matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity-matched analysis.

Population-Based Analysis of Completion Lymphadenectomy in Intermediate-Thickness Melanoma.

BACKGROUND: Multicenter selective lymphadenectomy trial 1 (MSLT-I) defined the prognostic and potential therapeutic values of sentinel lymph node biopsy (SLNB) for intermediate-thickness melanoma. The role of completion lymphadenectomy (CLND) is, however, unclear and the subject of the ongoing MSLT-II trial. METHODS: From 2003 to 2012, patients with tumors 1-4 mm thick with positive SLNB were identified in the Surveillance Epidemiology and End Results Program registry. The patients were divided into two groups: group 1 (CLND) and group 2 (observation). RESULTS: The study enrolled 2172 patients, the majority of whom were white and male with extremity primaries, no ulceration, Clark level 4 invasion, and nodes 2.01-4.0 mm deep. In the univariate analysis, CLND was associated with lower mean age, male gender, primary site, number of positive nodes, and geographic region (p < 0.05). In the multivariate analysis, male gender [odds ratio (OR), 1.27] and geographic area (Michigan OR, 2.31; Iowa OR, 1.69) were associated with CLND (p < 0.05). In the survival analysis, male gender, primary site, ulceration, Clark level, and depth and number of positive nodes were associated with survival (p < 0.05), but CLND was not (p = 0.83). In the Cox regression analysis, the relationship between male gender [hazard ratio (HR), 1.14], primary site trunk versus extremity (HR, 1.3), ulceration (HR, 1.79), Clark level (2 vs. 4 HR, 3.51; 2 vs. 5 HR, 6.48), depth (HR, 1.43) and number of nodes (1 vs. 2: HR, 1.23; 1 vs. ≥3: HR, 2.52) persisted (p < 0.05). However, when CLND was included in this model, it was not associated with improved survival. CONCLUSIONS: Age, gender, and geographic area predict the likelihood of CLND. In this retrospective study, CLND did not add survival benefit.

Impact of malnutrition on gastrointestinal surgical patients.

BACKGROUND: The accurate diagnosis of malnutrition is imperative if we are to impact outcomes in the malnourished. The American Society of Parenteral and Enteral Nutrition (ASPEN) and Academy of Nutrition and Dietetics (AND), in an attempt to address this issue, have provided evidence-based criteria to diagnose malnutrition. The purpose of this study was to validate the ASPEN/AND criteria in a cohort of patients from a single high-volume surgical oncology unit. METHODS: Patients undergoing major abdominal surgery from June 2013 to March 2015 were classified by their nutritional status using the ASPEN/AND criteria. RESULTS: A total of 490 patients were included. Median age was 64 y, a majority were female (50.6%), white (60.2%), underwent elective procedures (77.6%), had a Charlson comorbidity score (CCS) of 3-5 (40.0%), and a Clavien-Dindo complication (CDC) grade of 0-II (81.2%). A total of 93 (19.0%) patients were classified as moderately/severely malnourished. On univariate analysis, malnourished patients were more likely to be older, undergo emergent procedures, and have a CCS >5 (P < 0.05). Malnutrition was also associated with a longer postoperative length of stay (LOS), higher cost, higher in-hospital mortality, more severe complications, and higher readmission rates (P < 0.05). Multivariate analysis reaffirmed the association between malnutrition, LOS (odds ratio [OR] = 1.67), and cost (OR = 2.49), P < 0.05. Complications (OR = 1.35), mortality rates (OR = 3.05), and readmission rates (OR = 1.34) P > 0.05 failed to reach significance. CONCLUSIONS: Malnutrition worsens LOS and cost. Utilization of standardized criteria consistently identifies patients at risk of negative outcomes who may benefit from perioperative nutritional support.

Radiotherapy associated with improved survival for high-grade sarcoma of the extremity.

BACKGROUND: The impact of radiotherapy on local control in limb-preserving surgery for high-risk sarcoma has been well studied. However, the impact of the use and timing of radiation therapy on survival is unclear. METHODS: From 1988 to 2010, patients with Stage III extremity sarcoma were identified within the SEER registry and cohorts were created using propensity score matching between irradiated and non-irradiated groups. RESULTS: A total of 2,606 patients were identified, with a median age of 59 years a majority were white (81%), male (54%), received radiotherapy (78%), and had lower extremity (80%) sarcomas. The most common subtype was fibrohistiocytic (29.8%). Patients treated with radiotherapy were younger (57.2 vs. 60.3 years) and differed in subtype compared to those untreated. The matched cohorts were better balanced for all factors. Radiation therapy was associated with a 5% 5-year survival advantage on univariate analysis for both the unmatched (P = 0.002) and matched cohorts (P = 0.01). On multivariate analysis radiotherapy was associated with a 20% and 30% survival advantage for the matched and unmatched cohorts, respectively (P ≤ 0.02). The timing of radiotherapy did not affect survival. CONCLUSIONS: Radiotherapy, regardless of the timing, is associated with improved survival in high-risk sarcoma.

Assessment of health care cost for complex surgical patients: review of cost, re-imbursement and revenue involved in pancreatic surgery at a high-volume academic medical centre.

BACKGROUND: Pancreatic surgery is complex with the potential for costly hospitalization. METHODS: A retrospective review of patients undergoing a pancreatic resection was performed. RESULTS: The median age of the study population was 64 years. Half of the cohort was female (51%), and the majority were white (62%). Most patients underwent a pancreaticoduodenectomy (PD) (69%). The pre-operative age-adjusted Charlson comorbidity index was zero for 36% (n = 50), 1 for 31% (n = 43) and ≥2 for 33% (n = 45). The Clavien-Dindo grading system for post-operative complication was grade I in 17% (n = 24), whereas 45% (n = 62) were higher grades. The medians direct fixed, direct variable, fixed indirect and total costs were $2476, $15,397, $13,207 and $31,631, respectively. There was a positive contribution margin of $7108, whereas the net margin was a loss of $6790. On univariate analyses, age, type of operation and complication grade were associated with total cost (P ≤ 0.05), whereas operation type and complication grade were associated with a net margin (P = 0.01). These findings remained significant on multivariate analysis (P < 0.05). CONCLUSIONS: Increased cost, reimbursement and revenue were associated with type of operation and post-operative complications.

The influence of sentinel lymph node biopsy on survival for intermediate-thickness melanoma.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) failed to demonstrate a survival advantage for sentinel lymph node biopsy (SNB) in melanoma. This may have been secondary to inadequate statistical power. This study was designed to determine the impact of SNB on melanoma-specific survival (MSS) in a larger patient cohort. METHODS: From 2003-2008, patients with tumors 1-4 mm in thickness and clinically negative nodes were identified within the SEER registry. Propensity score was used to create two matched cohorts: those who underwent a wide excision with SNB or wide excision alone. RESULT: A total of 15,274 met inclusion criteria and 7,910 comprised the match cohort. Average age was 67.4 years. The majority were male (62.3 %) and white (97.2 %). Primary tumors were most frequently nonulcerated (77.1 %), located on the extremity (42.3 %), and T2 (64.1 %). There were 3,955 patients in both the SNB and observation groups. There was no significant difference in gender, ethnicity, ulceration status, primary site, or T-classification between the groups. Improved 5-year MSS was associated with SNB (85.7 vs. 84.0 %), female gender (88.3 vs. 82.7 %), absence of ulceration (87.5 vs. 75.7 %), extremity location (87.4 %), T2 disease (88.6 vs. 77.9 %), and a negative SNB (88.9 vs. 64.8 %). The relationships between observation [hazard ratio (HR) 1.18], male gender (HR 1.33), ulceration (HR 1.77), head-and-neck location (HR 1.34), and T3 disease (HR 1.82) persisted on multivariate analysis. CONCLUSIONS: Status of the sentinel node is the strongest predictor of survival in patients with intermediate thickness melanoma. SNB compared with observation was associated with a modest survival advantage.

Sentinel lymph node biopsy is associated with improved survival in Merkel cell carcinoma.

BACKGROUND: Although sentinel lymph node biopsy (SNB) has become a standard for Merkel cell carcinoma (MCC), the impact on survival is unclear. To better define the staging and therapeutic value of SNB, we compared SNB with nodal observation. METHODS: Patients with clinical stage I and II MCC in the Surveillance, Epidemiology, and End Results (SEER) registry undergoing surgery between 2003 and 2009 were identified and divided into two groups-SNB and observation. RESULTS: A total of 1,193 patients met the inclusion criteria (SNB 474 and Observation 719). The median age was 78 years, and the majority were White (95.3 %), male (58.8 %), received radiation therapy (52.9 %) and had T1 tumors (65.3 %). Twenty-four percent had a positive SNB. SNB patients were younger (73 vs. 81 years; p < 0.0001), had T1 tumors (69.6 vs. 62.5 %; p = 0.04) and received radiotherapy (57.8 vs. 40 %; p < 0.0001). Among biopsy patients, a negative SNB was associated with improved 5-year MCC-specific survival (84.5 vs. 64.6 %; p < 0.0001). Univariate analysis demonstrated an increased 5-year MCC-specific survival for the SNB group versus the Observation group (79.2 vs. 73.8 %; p = 0.004), female gender (83.2 vs. 70.4 %; p = 0.0004), and lower T stage (p < 0.0001). On Cox regression, diminished survival was noted for the Observation group (risk ratio [RR] 1.43; p = 0.04), male gender (RR 2.06; p < 0.0001), and a higher T stage. CONCLUSION: SNB for MCC provides prognostic information and is associated with a significant survival advantage.

The benefits of liver resection for non-colorectal, non-neuroendocrine liver metastases: a systematic review.

PURPOSE: Defining the benefits of resection of isolated non-colorectal, non-neuroendocrine (NCRNNE) liver metastases is difficult. To better understand the survival benefit in this group of patients, we conducted a systematic review of the previous literature. METHODS: Medline, Web of Knowledge, and manual searches were performed using search terms, such as "liver resection" and "primary tumor." Inclusion criteria were year>1990, >five patients, and median survival reported or derived. An expected median survival was calculated from weighted averages of median survivals, and differences were assessed using a permutation test. RESULTS: A total of 7,857 references were identified. Overall 4,735 abstracts were reviewed; 120 manuscripts evaluated and of these, 73 met the study inclusion criteria. The final population consisted of 3,596 patients with renal (n=234), ovarian (n=119), testicular (n=153), adrenal (n=90), small bowel (n=28), gallbladder (n=21), duodenum (n=38), gastric (n=481), pancreatic (n=55), esophageal (n=23), head and neck (n=15), and lung (n=36) cancers, gastrointestinal stromal tumors (GISTs) (n=106), cholangiocarcinoma (n=13), sarcoma (n=189), and melanoma (n=643). The greatest expected median was 63 months for genitourinary (GU) primaries (n=549; range 5.4-142 months) followed by 44.4 months for breast cancer (n=1,013; range 8-74 months), 22.3 months for gastrointestinal cancer (n=549; range 5-58 months), and 23.7 months for other tumor types (n=1,082; range 10-72 months). Using a permutation test, we observed that survival was best for patients with GU primaries followed by that for breast cancer patients. Additionally, we also observed that survival was similar for those with cancer of the GI tract and other primary sites. CONCLUSIONS: There appears to be a benefit to resection for patients with NCRNNE liver metastases. The degree of survival advantage is predicated by primary site.

Dendritic cell immunotherapy combined with gemcitabine chemotherapy enhances survival in a murine model of pancreatic carcinoma.

Pancreatic cancer is an extremely aggressive malignancy with a dismal prognosis. Cancer patients and tumor-bearing mice have multiple immunoregulatory subsets including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) that may limit the effectiveness of anti-tumor immunotherapies for pancreatic cancer. It is possible that modulating these subsets will enhance anti-tumor immunity. The goal of this study was to explore depletion of immunoregulatory cells to enhance dendritic cell (DC)-based cancer immunotherapy in a murine model of pancreatic cancer. Flow cytometry results showed an increase in both Tregs and MDSC in untreated pancreatic cancer-bearing mice compared with control. Elimination of Tregs alone or in combination with DC-based vaccination had no effect on pancreatic tumor growth or survival. Gemcitabine (Gem) is a chemotherapeutic drug routinely used for the treatment for pancreatic cancer patients. Treatment with Gem led to a significant decrease in MDSC percentages in the spleens of tumor-bearing mice, but did not enhance overall survival. However, combination therapy with DC vaccination followed by Gem treatment led to a significant delay in tumor growth and improved survival in pancreatic cancer-bearing mice. Increased MDSC were measured in the peripheral blood of patients with pancreatic cancer. Treatment with Gem also led to a decrease of this population in pancreatic cancer patients, suggesting that combination therapy with DC-based cancer vaccination and Gem may lead to improved treatments for patients with pancreatic cancer.

Immunotherapy for gastrointestinal malignancies.

BACKGROUND: Gastrointestinal (GI) cancers are the most common human tumors encountered worldwide. The majority of GI cancers are unresectable at the time of diagnosis, and in the subset of patients undergoing resection, few are cured. There is only a modest improvement in survival with the addition of modalities such as chemotherapy and radiation therapy. Due to an increasing global cancer burden, it is imperative to integrate alternative strategies to improve outcomes. It is well known that cancers possess diverse strategies to evade immune detection and destruction. This has led to the incorporation of various immunotherapeutic strategies, which enable reprogramming of the immune system to allow effective recognition and killing of GI tumors. METHODS: A review was conducted of the results of published clinical trials employing immunotherapy for esophageal, gastroesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers. RESULTS: Monoclonal antibody therapy has come to the forefront in the past decade for the treatment of colorectal cancer. Immunotherapeutic successes in solid cancers such as melanoma and prostate cancer have led to the active investigation of immunotherapy for GI malignancies, with some promising results. CONCLUSIONS: To date, monoclonal antibody therapy is the only immunotherapy approved by the US Food and Drug Administration for GI cancers. Initial trials validating new immunotherapeutic approaches, including vaccination-based and adoptive cell therapy strategies, for GI malignancies have demonstrated safety and the induction of antitumor immune responses. Therefore, immunotherapy is at the forefront of neoadjuvant as well as adjuvant therapies for the treatment and eradication of GI malignancies.

The use of isolated limb infusion in limb threatening extremity sarcomas.

UNLABELLED: This paper reports a single-institution experience with the use of isolated limb infusion for limb salvage in locally advanced, unresectable, recurrent limb threatening soft tissue sarcomas. BACKGROUND: Locally advanced, limb threatening soft tissue sarcomas (STS) pose a significant treatment challenge. We report our experience using isolated limb infusion (ILI) in patients with unresectable extremity STS. METHODS: A total of 22 patients with extremity STS underwent 26 ILIs with melphalan and dactinomycin. Patient characteristics, intra-operative parameters and toxicity were recorded. Outcome measures included limb-salvage and in-field response rates. RESULTS: Of the 19 lower and 7 upper extremity ILIs, Wieberdink grade III toxicity or less was observed in all. Median followup was 11 months. A total of 17 patients were evaluable at 3 months post-ILI with an overall response rate of 42%. Four (24%) had complete response (CR), three (18%) partial response (PR), three (18%) stable disease (SD) and seven (41%) progressive disease (PD). Twelve of 17 (71%) underwent successful limb preservation at a median of 9 months post-ILI. Two (12%) were downstaged to resectable disease and remain showing no evidence of disease (NED) after surgery at 30 and 22 months post-ILI. CONCLUSIONS: ILI is an attractive modality that provides regional disease control and limb preservation in patients with limb threatening sarcoma. Although short-term results appear encouraging, long-term follow-up is needed to fully assess the role of ILI in unresectable extremity STS.

Race-Related Differences in the Clinical Presentation and Histopathologic Features of Phyllodes Tumor.

BACKGROUND: Phyllodes tumor (PT) is a rare fibroepithelial lesion of the breast with variable malignant potential. Black women have a higher incidence of a related benign tumor, fibroadenoma, but there are limited epidemiological data on PT. The aim of our study was to evaluate race-related differences in the clinicopathologic features and outcomes of PT. METHODS: Our institutional pathology database was queried for breast specimen reports from 01/2009 to 10/2019 to identify patients with a pathologic diagnosis of PT. Chart review and detailed slide review were performed to obtain clinical and histopathologic variables, respectively. RESULTS: Among twelve patients, two had malignant PT, three had borderline PT, and seven had benign PT. All patients with malignant and borderline PT were black, compared with 29% of those with benign PT. There were no apparent race-related differences in specific histopathologic features among black vs. non-black women with benign PT. Malignant and borderline PT were relatively larger than benign PT, with mean tumor sizes of 9.0 cm (standard deviation [SD] 4.7 cm), 12.2 cm (SD 9.4 cm), and 5.4 cm (SD 5.8 cm), respectively. Two women had a local recurrence, both of whom were black. DISCUSSION: In this single-institution retrospective study, we observed disproportionate rates of aggressive histopathologic features and disparate outcomes among black women with PT. A multi-institutional PT registry would facilitate improved knowledge about race-related differences in the presentation and outcomes of this rare tumor.

Pan-tissue mitochondrial phenotyping reveals lower OXPHOS expression and function across cancer types.

Targeting mitochondrial oxidative phosphorylation (OXPHOS) to treat cancer has been hampered due to serious side-effects potentially arising from the inability to discriminate between non-cancerous and cancerous mitochondria. Herein, comprehensive mitochondrial phenotyping was leveraged to define both the composition and function of OXPHOS across various murine cancers and compared to both matched normal tissues and other organs. When compared to both matched normal tissues, as well as high OXPHOS reliant organs like heart, intrinsic expression of the OXPHOS complexes, as well as OXPHOS flux were discovered to be consistently lower across distinct cancer types. Assuming intrinsic OXPHOS expression/function predicts OXPHOS reliance in vivo, these data suggest that pharmacologic blockade of mitochondrial OXPHOS likely compromises bioenergetic homeostasis in healthy oxidative organs prior to impacting tumor mitochondrial flux in a clinically meaningful way. Although these data caution against the use of indiscriminate mitochondrial inhibitors for cancer treatment, considerable heterogeneity was observed across cancer types with respect to both mitochondrial proteome composition and substrate-specific flux, highlighting the possibility for targeting discrete mitochondrial proteins or pathways unique to a given cancer type.