Faculty Bibliography

BACKGROUND:Breast cancer and hepatitis C virus (HCV) infection are major health problems in the U.S. Despite these highly prevalent diseases, there is limited information on the effect of HCV infection among patients with breast cancer receiving chemotherapy and the potential challenges they face during treatment. Currently, there are no guidelines for chemotherapy administration in HCV-positive patients with breast cancer. MATERIALS AND METHODS:We performed a retrospective case-control analysis on six patients with breast cancer with active HCV infection and 12 HCV-negative matched controls who received chemotherapy between January 2000 and April 2015. We investigated dose delays, dose changes, hospitalization, hematologic reasons for dose delays, and variation in blood counts during chemotherapy from the patients' medical records. Fisher's exact test was used for statistical comparison of the outcome variables between the two groups. RESULTS:When compared with the HCV-negative patients, the HCV-positive group was at a significantly higher risk of dose delays (100% vs. 33%, p value .013), dose changes (67% vs. 8%, p value .022), hospitalization during chemotherapy (83% vs. 25%, p value .043), and hematotoxicity related dose delays (83% vs. 8%, p value .003). HCV-positive patients took a longer time to complete treatment than the HCV-negative group. CONCLUSION:Patients with HCV receiving chemotherapy for breast cancer are more likely to experience complications such as dose delays, dose modifications, and hospitalization. Future studies to confirm our findings and investigate on the effect of concurrent HCV and breast cancer treatment are warranted. IMPLICATIONS FOR PRACTICE:This study found that hepatitis C infection is associated with a greater risk of treatment delays and dose modifications in patients with breast cancer receiving cytotoxic chemotherapy. Hepatitis C-positive patients have a higher treatment burden with dose changes, hospitalizations, and longer treatment periods than noninfected patients. Further prospective investigations to confirm these findings are warranted in a larger patient population. Given that hepatitis C infection can be curable with direct-acting antivirals, treatment of hepatitis C may alleviate treatment challenges during chemotherapy and improve survival for patients with breast cancer.

Disparities in outcomes for vulnerable women is an ongoing problem. Homelessness and breast cancer treatment outcomes is understudied. This is a descriptive study exploring types of homelessness and treatment delays at an urban safety net hospital providing care to a vulnerable patient population.This study is a retrospective chart review of homeless female patients diagnosed with breast cancer between January 1, 2000 and December 31, 2014. Data for this study were acquired from the hospital cancer registry and electronic medical record. All demographic characteristics, time to treatment and factors related to delays to treatment were analyzed descriptively, reporting frequencies and proportions. The total number of individuals analyzed was 24. All except two subjects were delayed to treatment (≥ 30 days from diagnosis to treatment). Most women in this cohort were categorized as chronically homeless (46%) with the rest categorized as transitionally (29%) or episodically (12%) homeless. The majority of subjects (70%) were Black, non-Hispanic. All except one subject were publicly insured (71% Medicaid; 12% Medicare) or uninsured (8%). Regardless of type of homelessness, most subjects were either 30-60 or 60-90 days delayed. Those who were chronically homeless experienced significantly more delays to first treatment (56% of those who were delayed 30-60 days and 57% of those who were delayed 60-90 days; p value 0.006) than those who were episodically or transitionally homeless. Significant delays and barriers to breast cancer treatment exist among women experiencing homelessness. Further studies to improve breast cancer care for homeless women are warranted.

BACKGROUND:Venous thromboembolism (VTE) prophylaxis has become routine for patients undergoing most operations, but it remains controversial for breast operations due to a perceived low risk of VTE. There is limited evidence to support routine or extended VTE prophylaxis in breast surgery. We investigated the benefits and risks of the Caprini risk stratification tool and corresponding prevention program, including extended prophylaxis for high-risk groups, in patients undergoing operations for benign and malignant breast lesions. STUDY DESIGN:Using Boston Medical Center data, we reviewed records of patients who underwent lumpectomy or total mastectomy (with or without axillary surgery and/or reconstruction), between 2011 and 2018, to collect information about operation, Caprini score, administration of prophylaxis, and postoperative VTE or bleeding events. Descriptive statistics were performed. RESULTS:Seven hundred fifty patients underwent 881 operations; 48.9% were at low or moderate risk of VTE, 43.8% were at high risk, and 7.3% were at highest risk. There were no VTE events in the low- and moderate-risk groups, 5 (1.3%) in the high-risk, and 1 (1.6%) in the highest-risk group. One patient was diagnosed with VTE during hospitalization. None of the 5 patients who developed VTE after discharge was prescribed the recommended extended chemoprophylaxis. There were 19 bleeding events that did not require reoperation; 3 patients returned to the operating room. There was no correlation of bleeding with receipt of extended chemoprophylaxis. CONCLUSIONS:The Caprini protocol can identify high-risk breast surgery patients who may benefit from extended VTE chemoprophylaxis, as well as low-risk patients who require no chemoprophylaxis. Furthermore, administration of extended chemoprophylaxis was not associated with an increased risk of bleeding.

PURPOSE/OBJECTIVE:To examine the impact of pre-diagnosis depressive symptoms and mental health-related quality of life (HRQOL) on survival among older patients with multiple myeloma (MM). METHODS:We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data resource. Patients aged 65 years and older diagnosed with first primary MM between 1998 and 2014 were identified, and presence of depressive symptoms was determined based on responses to 3 depression screening questions prior to MM diagnosis. Veterans RAND 12 mental component summary (MCS) scores were analyzed to evaluate mental HRQOL. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of all-cause and cancer-specific mortality. RESULTS:Of 522 patients, mean (SD) age at diagnosis was 76.9 (6.1) years and 158 (30%) reported depressive symptoms. Patients with depressive symptoms had a higher number of comorbid conditions and nearly all (84%) scored below the median MCS. Pre-diagnosis depressive symptoms were not associated with all-cause (HR = 1.01, 95% CI 0.79-1.29) or cancer-specific mortality (HR = 0.94, 95% CI 0.69-1.28). MM patients scoring in the second MCS tertile (vs the highest tertile) had a modestly increased risk of all-cause (HR = 1.19, 95% CI 0.91-1.55) and cancer-specific mortality (HR = 1.17, 95% CI 0.86-1.60), but these estimates were not statistically significant. CONCLUSION/CONCLUSIONS:Pre-diagnosis depressive symptoms and lower mental HRQoL did not impact survival among older MM patients. Highly prevalent depressive symptoms among older MM patients deserve clinical attention. Such efforts can inform clinicians in tailoring care for this vulnerable population.

IMPORTANCE:Compared with non-Hispanic white women, racial/ethnic minority women receive a diagnosis of breast cancer at a more advanced stage and have higher morbidity and mortality with breast cancer diagnosis. Access to care with adequate insurance may be associated with earlier diagnosis, expedited treatment, and improved prognosis. OBJECTIVE:To examine the extent to which insurance is associated with access to timely breast cancer diagnosis and breast cancer stage differences among a large, diverse population of US patients with breast cancer. DESIGN, SETTING, AND PARTICIPANTS:This retrospective, cross-sectional population-based study used data from the Surveillance, Epidemiology, and End Results Program on 177 075 women aged 40 to 64 years who received a diagnosis of stage I to III breast cancer between January 1, 2010, and December 31, 2016. Statistical analysis was performed from August 1, 2017, to October 1, 2019. MAIN OUTCOMES AND MEASURES:The primary outcome was the risk of having a more advanced stage of breast cancer at diagnosis (ie, stage III vs stages I and II). Mediation analyses were conducted to determine associations of race/ethnicity and proportion of observed differences mediated by health insurance status with earlier stage of diagnosis. RESULTS:A total of 177 075 women (mean [SD] age, 53.5 [6.8] years; 148 124 insured and 28 951 uninsured or receiving Medicaid) were included in the study. A higher proportion of women either receiving Medicaid or who were uninsured received a diagnosis of locally advanced breast cancer (stage III) compared with women with health insurance (20% vs 11%). In multivariable models, non-Hispanic black (odds ratio [OR], 1.46 [95% CI, 1.40-1.53]), American Indian or Alaskan Native (OR, 1.31 [95% CI, 1.07-1.61]) and Hispanic (OR, 1.35 [95% CI, 1.30-1.42]) women had higher odds of receiving a diagnosis of locally advanced disease (stage III) compared with non-Hispanic white women. When adjusting for health insurance and other socioeconomic factors, associations between race/ethnicity and risk of locally advanced breast cancer were attenuated (non-Hispanic black: OR, 1.29 [95% CI, 1.23-1.35]; American Indian or Alaskan Native: OR, 1.11 [95% CI, 0.91-1.35]; Hispanic: OR, 1.17 [95% CI, 1.12-1.22]). Nearly half (45%-47%) of racial differences in the risk of locally advanced disease were mediated by health insurance. CONCLUSIONS AND RELEVANCE:This study's findings suggest that nearly half of the observed racial/ethnic disparities in higher stage at breast cancer diagnosis are mediated by health insurance coverage.

BACKGROUND:Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedback about treatment response at the earliest stages of therapy to identify patients likely to benefit from changing treatment. Diffuse optical spectroscopic imaging (DOSI) has emerged as a promising functional imaging technique for NAC monitoring. DOSI uses non-ionizing near-infrared light to provide non-invasive measures of absolute concentrations of tissue chromophores such as oxyhemoglobin. In 2011, we reported a new DOSI prognostic marker, oxyhemoglobin flare: a transient increase in oxyhemoglobin capable of discriminating NAC responders within the first day of treatment. In this follow-up study, DOSI was used to confirm the presence of the flare as well as to investigate whether DOSI markers of NAC response are regimen dependent. METHODS:This dual-center study examined 54 breast tumors receiving NAC measured with DOSI before therapy and the first week following chemotherapy administration. Patients were treated with either a standard of care maximum tolerated dose (MTD) regimen or an investigational metronomic (MET) regimen. Changes in tumor chromophores were tracked throughout the first week and compared to pathologic response and treatment regimen at specific days utilizing generalized estimating equations (GEE). RESULTS:Within patients receiving MTD therapy, the oxyhemoglobin flare was confirmed as a prognostic DOSI marker for response appearing as soon as day 1 with post hoc GEE analysis demonstrating a difference of 48.77% between responders and non-responders (p < 0.0001). Flare was not observed in patients receiving MET therapy. Within all responding patients, the specific treatment was a significant predictor of day 1 changes in oxyhemoglobin, showing a difference of 39.45% (p = 0.0010) between patients receiving MTD and MET regimens. CONCLUSIONS:DOSI optical biomarkers are differentially sensitive to MTD and MET regimens at early timepoints suggesting the specific treatment regimen should be considered in future DOSI studies. Additionally, DOSI may help to identify regimen-specific responses in a more personalized manner, potentially providing critical feedback necessary to implement adaptive changes to the treatment strategy.

UNLABELLED:The size distribution of adipocytes in fat tissue provides important information about metabolic status and overall health of patients. Histological measurements of biopsied adipose tissue can reveal cardiovascular and/or cancer risks, to complement typical prognosis parameters such as body mass index, hypertension or diabetes. Yet, current methods for adipocyte quantification are problematic and insufficient. Methods such as hand-tracing are tedious and time-consuming, ellipse approximation lacks precision, and fully automated methods have not proven reliable. A semi-automated method fills the gap in goal-directed computational algorithms, specifically for high-throughput adipocyte quantification. Here, we design and develop a tool, AdipoCyze, which incorporates a novel semi-automated tracing algorithm, along with benchmark methods, and use breast histological images from the Komen for the Cure Foundation to assess utility. Speed and precision of the new approach are superior to conventional methods and accuracy is comparable, suggesting a viable option to quantify adipocytes, while increasing user flexibility. This platform is the first to provide multiple methods of quantification in a single tool. Widespread laboratory and clinical use of this program may enhance productivity and performance, and yield insight into patient metabolism, which may help evaluate risks for breast cancer progression in patients with comorbidities of obesity. ABBREVIATIONS:BMI: body mass index.

BACKGROUND:The differential occurrence of second primary cancers by race following ovarian cancer is poorly understood. Our objective was to determine the incidence of second primary gynecologic cancers (SPGC) following definitive therapy for ovarian cancer. Specifically, we aimed to determine differences in SPGC incidence by Asian ethnic subgroups. METHODS:We identified 27,602 women ages 20 years and older and diagnosed with first primary epithelial ovarian cancer between 2000 and 2016 who received surgery and chemotherapy in 18 population-based Surveillance, Epidemiology and End Results Program registries. We compared the incidence of SPGC with expected incidence rates in the general population of women using estimated standardized incidence ratios (SIR) and 95% confidence intervals (CI). RESULTS:The incidence of SPGC was lower among White women (SIR = 0.73; 95% CI, 0.59-0.89), and higher among Black (SIR = 1.80; 95% CI, 0.96-3.08) and Asian/Pacific Islander (API) women (SIR = 1.83; 95% CI, 1.07-2.93). Increased risk of vaginal cancers was observed among all women, although risk estimates were highest among API women (SIR = 26.76; 95% CI, 5.52-78.2) and were also significant for risk of uterine cancers (SIR = 2.53; 95% CI, 1.35-4.33). Among API women, only Filipinas had significantly increased incidence of SPGC overall including both uterine and vaginal cancers. CONCLUSIONS:Risk of SPGC following treatment of ovarian cancer differs by race and ethnicity, with Filipina women having the highest rates of second gynecologic cancers among Asian women. IMPACT:Ensuring access and adherence to surveillance may mitigate ethnic differences in the early detection and incidence of second gynecologic cancers.

PURPOSE/OBJECTIVE:Genomic testing in early-stage hormone-positive breast cancer is the standard of care. However, decisions based on genomic testing results are predicated on the assumption that patients receive endocrine treatment. We sought to investigate racial differences in genomic testing and adjuvant treatment in breast cancer. METHODS:A retrospective, population-based hospital registry study using the National Cancer Database. Participants included women with stages I-II, ER + breast cancer between 2010 and 2014. Sociodemographic factors were analyzed. Primary outcomes were the utilization of genomic testing and receipt of endocrine therapy. Logistic regression modeling was used to compute crude and adjusted odds of genomic testing and receipt of endocrine therapy. RESULTS:Among a total sample size of 387,008 patients, 147,863 (38.2%) underwent genomic testing. Older age (≥ 70 years) was associated with a lower adjusted odd of genomic testing (OR 0.33; 95% CI 0.32-0.34, p =  < 0.0001). Black patients had lower odds of receiving genomic testing on multivariate analysis compared to Whites (OR 0.82; 95% CI 0.80-0.85, p =  < 0.0001). In patients who underwent a genomic test, compared to Whites, Blacks had a lower odds of receiving endocrine therapy (OR 0.86; 95% CI 0.80-0.93, p =  < 0.0001) even if they did not receive adjuvant chemotherapy (OR 0.90; 95% CI 0.82-0.98, p = 0.014). CONCLUSIONS:In a national sample of breast cancer patients, Black women are less likely to get genomic testing and receive hormonal therapy, even when adjuvant chemotherapy is omitted. A priority in addressing breast cancer disparities is to ensure adherence to hormonal therapy among all women, including those who do not receive adjuvant chemotherapy.

PURPOSE/OBJECTIVE:Patient-reported outcomes such as self-reported health (SRH) are important in understanding quality cancer care, yet little is known about links between SRH and outcomes in older patients with multiple myeloma (MM). We evaluated associations between SRH and mortality among older patients with MM. METHODS:We analyzed a retrospective cohort of patients ages ≥ 65 years diagnosed with first primary MM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) data resource. Pre-diagnosis SRH was grouped as high (excellent/very good/good) or low (fair/poor). We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between SRH and all-cause and MM-specific mortality. RESULTS:Of 521 MM patients with mean (SD) age at diagnosis of 76.8 (6.1) years, 32% reported low SRH. In multivariable analyses, low SRH was suggestive of modest increased risks of all-cause mortality (HR 1.32, 95% CI 1.02-1.71) and MM-specific mortality (HR 1.22, 95% CI 0.87-1.70) compared to high SRH. CONCLUSION/CONCLUSIONS:Findings suggest that low pre-diagnosis SRH is highly prevalent among older patients with MM and is associated with modestly increased all-cause mortality. Additional research is needed to address quality of life and modifiable factors that may accompany poor SRH in older patients with MM.