Faculty Bibliography

PURPOSE/OBJECTIVE:There are approximately 150,000 women living with metastatic breast cancer (mBC) in the United States. Disparities in de novo mBC incidence and mortality exist across race/ethnicity, socioeconomic status (SES), and rurality. However, how SES and rurality independently impact mBC outcomes across different racial/ethnic groups is not fully understood. The purpose of this study was to determine the impact of SES and rurality on cancer-specific mortality among women with mBC by race/ethnicity. METHODS:We conducted a large, population-based retrospective cohort study in women aged 18 + years diagnosed with de novo mBC using the Surveillance, Epidemiology and End Results Census Tract-level SES and Rurality Database (2000-2015). Associations between SES/rurality and cancer-specific mortality were determined using Fine and Gray regression models. Subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) by race/ethnicity and hormone receptor (HR) status were calculated. RESULTS:A cohort of 33,976 women were included with the majority being White (67%), 17% Black, 0.4% American Indian/Alaskan Native, 6% Asian/Pacific Islander, and 10% Latina/Hispanic. We observed the greatest increased risk of BC mortality among Black women with HR-negative mBC residing in neighborhoods with lower SES (lowest versus highest quintile: SHR 1.38, 95% CI 1.00-1.90) and in rural areas compared to urban areas (SHR 1.27, 95% CI 1.01-1.59). CONCLUSION/CONCLUSIONS:Overall, BC-specific survival among women with de novo mBC differs by race/ethnicity, with the greatest adverse impacts of SES and rurality affecting Black women with HR-negative disease.

OBJECTIVE:To understand the role of racial residential segregation on Black-White disparities in breast cancer presentation, treatment, and outcomes. SUMMARY OF BACKGROUND DATA:Racial disparities in breast cancer treatment and outcomes are well documented. Black individuals present at advanced stage, are less likely to receive appropriate surgical and adjuvant treatment, and have lower overall and stage-specific survival relative to White individuals. METHODS:Using data from the Surveillance, Epidemiology, and End Results program, we performed a retrospective cohort study of Black and White patients diagnosed with invasive breast cancer from 2005 to 2015 within the 100 most populous participating counties. The racial index of dissimilarity was used as a validated measure of residential segregation. Multivariable regression was performed, predicting advanced stage at diagnosis (stage III/IV), surgery for localized disease (stage I/II), and overall stage-specific survival. RESULTS:After adjusting for age at diagnosis, estrogen/progesterone receptor status, and region, Black patients have a 49% greater risk (relative risk [RR] 1.49 95% confidence interval [CI] 1.27, 1.74) of presenting at advanced stage with increasing segregation, while there was no observed difference in Whites (RR 1.04, 95% CI 0.93, 1.16). Black patients were 3% less likely to undergo surgical resection for localized disease (RR 0.97, 95% CI 0.95, 0.99) with increasing segregation, while Whites saw no significant difference. Black patients had a 29% increased hazard of death (RR 1.29, 95% CI 1.04, 1.60) with increasing segregation; there was no significant difference among White patients. CONCLUSIONS:Our data suggest that residential racial segregation has a significant association with Black-White racial disparities in breast cancer. These findings illustrate the importance of addressing structural racism and residential segregation in efforts to reduce Black-White breast cancer disparities.

PURPOSE:Hospital readmissions occur commonly in those receiving cancer care and result in impaired quality of life and increased costs. Causes of readmission in safety net hospitals that serve vulnerable populations are not well understood. The primary goal of this project was to identify potentially avoidable and intervenable causes of readmissions to an urban safety net hospital. METHODS:A retrospective chart review was performed on patients who were readmitted within 30 days of discharge from the hematology and oncology service at Boston Medical Center over the 6-month period between October 2018 and March 2019. Charts were reviewed by three internal medicine residents and discussed under the supervision of an attending oncologist. RESULTS:Two hundred ninety-one patient encounters involving 203 unique patients were identified in the 6-month study period. Of these 291 encounters, 80 encounters (27.5%) were followed by a readmission within 30 days and occurred in 61 (30.0%) unique patients. Nineteen (31.1%) of these 61 patients experienced two readmissions within 30 days of discharge. Twenty-five readmissions (31.3%) were classified as potentially avoidable, with the most common cause of potentially avoidable readmissions attributed to ascitic or pleural fluid reaccumulation (8, 32%). The majority of presumed nonpreventable readmissions were due to expected complications of cancer progression and treatment-related side effects. DISCUSSION:In conclusion, readmissions were common, and a modifiable reason for 30-day readmissions was identified. Addressing recurrent ascitic and pleural fluid reaccumulation in the outpatient setting could help to reduce inpatient hospital readmission on an inpatient oncology service.

PURPOSE:Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM. METHODS:We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011. Patients were identified using the SEER-Medicare linked database and followed through December 2013. Cumulative incidences of IV bisphosphonate initiation and time to discontinuation among users were compared between racial and ethnic groups. In Fine and Gray competing risk models, we estimated subdistribution hazard ratios (SHRs) and 95% CIs for initiation and discontinuation. RESULTS:We included 14,231 eligible patients with MM (median age, 76 years; 52% male). Over a median follow-up of 23.1 months, 54% of patients received at least one IV bisphosphonate dose. Our final analytical sample included 10,456 non-Hispanic (NH) Whites, 2,267 NH Blacks, 548 Asian and Pacific islanders, and 815 Hispanic and Latino patients. A higher proportion of White patients (56.1%) newly received IV bisphosphonates after MM diagnosis compared with NH Blacks (45.4%). Compared with White patients, NH Black patients were less likely to initiate IV bisphosphonates (SHR, 0.74; 95% CI, 0.70 to 0.79) and slightly more likely to discontinue treatment (SHR, 1.10; 95% CI, 1.01 to 1.19). CONCLUSION:Approximately half of the patients with MM of age ≥ 65 years did not receive IV bisphosphonates, with significant delay among racial minority groups. These findings highlight the need for improvement of IV bisphosphonate uptake in patients with MM of age ≥ 65 years.

IMPORTANCE/OBJECTIVE:Given the widespread use of the 21-gene recurrence score for identifying candidates for adjuvant chemotherapy, it is important to examine the performance of the Oncotype DX Breast Recurrence Score test in diverse patient populations to validate this approach for tailoring treatment in women in racial/ethnic minority groups. OBJECTIVE:To examine whether breast cancer-specific mortality for women with hormone-dependent breast cancer differs by race/ethnicity across risk categories defined by the Oncotype DX Breast Recurrence Score test and whether the prognostic accuracy of the 21-gene recurrence score differs by race/ethnicity. DESIGN, SETTING, AND PARTICIPANTS/METHODS:This retrospective, population-based cohort study used the Surveillance, Epidemiology, and End Results Oncotype DX 2004-2015 database to obtain breast cancer-specific survival data on US women 18 years and older who were diagnosed with first primary stage I to III, estrogen receptor-positive breast cancer between January 1, 2004, and December 31, 2015, and had tumor testing through the Genomic Health Clinical Laboratory. Data were analyzed from April 20 to September 27, 2020. MAIN OUTCOMES AND MEASURES/METHODS:The primary outcome was breast cancer-specific mortality among women from different racial/ethnic groups stratified by the 21-gene recurrence score risk categories. Secondary analyses compared the prognostic accuracy of the recurrence score among the different racial/ethnic groups. RESULTS:A total of 86 033 patients with breast cancer (mean [SD] age, 57.6 [10.6] years) with Oncotype DX Breast Recurrence Score test information were available for the analysis, including 64 069 non-Hispanic White women (74.4%), 6719 non-Hispanic Black women (7.8%), 7944 Hispanic women (9.2%), 6950 Asian/Pacific Islander women (8.0%), and 351 American Indian/Alaska Native women (0.4%). Black women were significantly more likely than non-Hispanic White women to have a recurrence score greater than 25 (17.7% vs 13.7%; P < .001). Among women with axillary node-negative tumors, competing risk models adjusted for age, tumor characteristics, and treatment found higher breast cancer-specific mortality for Black compared with non-Hispanic White women within each recurrence score risk stratum, with subdistribution hazard ratios of 2.54 (95% CI, 1.44-4.50) for Black women with recurrence scores of 0 to 10, 1.64 (95% CI, 1.23-2.18) for Black women with recurrence scores of 11 to 25, and 1.48 (95% CI, 1.10-1.98) for Black women with scores greater than 25. The prognostic accuracy of the recurrence score was significantly lower for Black women, with a C index of 0.656 (95% CI, 0.592-0.720) compared with 0.700 (95% CI, 0.677-0.722) (P = .002) for non-Hispanic Whites. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:In this cohort study, Black women in the US were more likely to have a high-risk recurrence score and to die of axillary node-negative breast cancer compared with non-Hispanic White women with comparable recurrence scores. The Oncotype DX Breast Recurrence Score test has lower prognostic accuracy in Black women, suggesting that genomic assays used to identify candidates for adjuvant chemotherapy may require model calibration in populations with greater racial/ethnic diversity.

SIGNIFICANCE:Diffuse optical imaging (DOI) provides in vivo quantification of tissue chromophores such as oxy- and deoxyhemoglobin (HbO2 and HHb, respectively). These parameters have been shown to be useful for predicting neoadjuvant treatment response in breast cancer patients. However, most DOI devices designed for the breast are nonportable, making frequent longitudinal monitoring during treatment a challenge. Furthermore, hemodynamics related to the respiratory cycle are currently unexplored in the breast and may have prognostic value. AIM:To design, fabricate, and validate a high optode-density wearable continuous wave diffuse optical probe for the monitoring of breathing hemodynamics in breast tissue. APPROACH:The probe has a rigid-flex design with 16 dual-wavelength sources and 16 detectors. Performance was characterized on tissue-simulating phantoms, and validation was performed through flow phantom and cuff occlusion measurements. The breasts of N  =  4 healthy volunteers were measured while performing a breathing protocol. RESULTS:The probe has 512 unique source-detector (S-D) pairs that span S-D separations of 10 to 54 mm. It exhibited good performance characteristics: μa drift of 0.34%/h, μa precision of 0.063%, and mean SNR  ≥  24  dB up to 41 mm S-D separation. Absorption contrast was detected in flow phantoms at depths exceeding 28 mm. A cuff occlusion measurement confirmed the ability of the probe to track expected hemodynamics in vivo. Breast measurements on healthy volunteers during paced breathing revealed median signal-to-motion artifact ratios ranging from 8.1 to 8.7 dB. Median ΔHbO2 and ΔHHb amplitudes ranged from 0.39 to 0.67  μM and 0.08 to 0.12  μM, respectively. Median oxygen saturations at the respiratory rate ranged from 82% to 87%. CONCLUSIONS:A wearable diffuse optical probe has been designed and fabricated for the measurement of breast tissue hemodynamics. This device is capable of quantifying breathing-related hemodynamics in healthy breast tissue.

PURPOSE/OBJECTIVE:Frailty is assessed when making treatment decisions among older women with breast cancer (BC), which in turn impacts survival. We evaluated associations between pre-diagnosis frailty and risks of BC-specific and all-cause mortality in older women. METHODS:We conducted a retrospective cohort study of Medicare beneficiaries ages ≥ 65 years with stage I-III BC using the Surveillance, Epidemiology and End Results-Medicare Health Outcome Survey Data Resource. Frailty was measured using the deficit-accumulation frailty index, categorized as robust, pre-frail, or frail, at baseline and during follow-up. Fine and Gray competing risk and Cox proportional hazards models were used to estimate subdistribution hazard ratios (SHR) and hazard ratios (HR) with 95% confidence intervals (CI) for BC-specific and all-cause mortality, respectively. RESULTS:Among 2411 women with a median age of 75 years at BC diagnosis, 49.5% were categorized as robust, 29.4% were pre-frail and 21.1% were frail. Fewer frail women compared to robust women received breast-conserving surgery (52.8% vs. 61.5%, frail vs. robust, respectively) and radiation (43.5% vs. 51.8%). In multivariable analyses, degree of frailty was not associated with BC-specific mortality (frail vs robust SHR 1.47, 95% CI 0.97-2.24). However, frail women with BC had higher risks of all-cause mortality compared to robust women with BC (HR 2.32, 95% CI 1.84-2.92). CONCLUSION/CONCLUSIONS:Among a cohort of older women with BC, higher degrees of frailty were associated with higher risk of all-cause mortality, but not BC-specific mortality. Future study should examine if preventing progression of frailty may improve all-cause mortality.

This cohort study examines the risk of skeletal-related events associated with the frequency of bisphosphonate treatment in patients with multiple myeloma.

BACKGROUND:Multiple independent risk factors are associated with the prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), the most common BC subtype. This study describes U.S. population-based recurrence rates among older, resected women with HR+/HER2- early BC. METHODS:We conducted a retrospective cohort study of older women diagnosed with incident, invasive stages I-III HR+/HER2- BC who underwent surgery to remove the primary tumor using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database (2007-2015). SEER records and administrative health claims data were used to ascertain patient and tumor-specific characteristics, treatment, and frailty status. Cumulative incidences of BC recurrence were estimated using a validated algorithm for administrative claims data. Multivariable Fine-Gray competing risk models estimated adjusted subdistribution hazards ratios and 95 % confidence intervals for associations with BC recurrence risk. RESULTS:Overall, 46,027 women age ≥65 years were included in our analysis. Over a median follow up of 7 years, 6531 women experienced BC recurrence with an estimated 3 and 5-year cumulative incidence rates of 10 % and 16 %, respectively. Higher 3- and 5-year cumulative incidences were observed in women with larger tumor size (5+ cm, 21 % and 28 %), lymph node involvement (4+ nodes, 27 % and 37 %), and with frail health status at diagnosis (13 % and 20 %). Independent of these clinical risk factors, Black, Hispanic and American Indian/Alaskan Native women had significantly increased BC recurrence risks. CONCLUSIONS:Rates of recurrence in HR+/HER2- early BC differs by several patient and clinical factors, including high-risk tumor characteristics. Racial differences in BC outcomes deserve continued attention from clinicians and policymakers.

Hepatocellular carcinoma commonly metastasizes to organs, but there are few reports of vertebral metastases causing cord compression. Here, we present a case of thoracic cord compression in a patient with advanced hepatocellular carcinoma. Providers' and patient's awareness of this risk is important, as this is an oncological emergency.