Women under 40 years old are at increased risk for developing human epidermal growth factor receptor 2 (HER2) positive or triple negative subtype and more advanced breast cancer, yet young age itself ...has also historically been an independent prognostic factor.
Using the Surveillance, Epidemiology, and End Results (SEER) Program, we examined data for 271,173 women with stage I-III breast cancer between 2010 and 2015. Using Fine and Gray regression models to account for competing risks, we examined the risk of breast cancer-specific death by age and clinical subtypes, considering grade, hormone receptor (HR) and HER2 status, adjusting for demographic, clinical and treatment variables.
Of 271,173 women eligible for analysis, 14,109 were <40 years of age. Women under 40 years old were more likely to be non-white, uninsured, and to have higher stage, higher grade, HER2-positive and triple-negative subtype disease (all, p < 0.001). Compared to women ages 40–60, women ages <40 had higher breast cancer mortality (hazard ratio, 1.8; 95% confidence interval (CI) 1.6–1.9) in unadjusted analysis. In models controlling for demographic, clinical and treatment factors, young age was significantly associated with an increased risk of breast cancer mortality among women with HR-positive, lower grade disease (hazard ratio 1.7; 95% CI 1.4–2.1) but not for women with high grade/HR-positive, HER2-positive, or triple-negative disease. Women age >75 had increased breast cancer mortality in all subtypes.
With modern clinical subtyping, age under 40 remains independently associated with worse outcomes in 30 months follow-up only in HR-positive, lower grade disease.
•Young women present with more advanced and aggressive types of breast cancer.•Young age is not an independent prognostic factor in HER2+ breast cancer or TNBC.•Young age is independently associated with poor outcomes in HR+/lower grade disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every ...country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence‐based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real‐world data.
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To update and examine national temporal trends in contralateral prophylactic mastectomy (CPM) and determine whether survival differed for invasive breast cancer patients based on hormone receptor ...(HR) status and age.
We identified women diagnosed with unilateral stage I to III breast cancer between 1998 and 2012 within the Surveillance, Epidemiology, and End Results registry. We compared characteristics and temporal trends between patients undergoing breast-conserving surgery, unilateral mastectomy, and CPM. We then performed Cox proportional-hazards regression to examine breast cancer-specific survival (BCSS) and overall survival (OS) in women diagnosed between 1998 and 2007, who underwent breast-conserving surgery with radiation (breast-conserving therapy), unilateral mastectomy, or CPM, with subsequent subgroup analysis stratifying by age and HR status.
Of 496,488 women diagnosed with unilateral invasive breast cancer, 59.6% underwent breast-conserving surgery, 33.4% underwent unilateral mastectomy, and 7.0% underwent CPM. Overall, the proportion of women undergoing CPM increased from 3.9% in 2002 to 12.7% in 2012 (P < 0.001). Reconstructive surgery was performed in 48.3% of CPM patients compared with only 16.0% of unilateral mastectomy patients, with rates of reconstruction with CPM rising from 35.3% in 2002 to 55.4% in 2012 (P < 0.001). When compared with breast-conserving therapy, we found no significant improvement in BCSS or OS for women undergoing CPM (BCSS: HR 1.08, 95% confidence interval 1.01-1.16; OS: HR 1.08, 95% confidence interval 1.03-1.14), regardless of HR status or age.
The use of CPM more than tripled during the study period despite evidence suggesting no survival benefit over breast conservation. Further examination on how to optimally counsel women about surgical options is warranted.
OBJECTIVE:To update and examine national temporal trends in contralateral prophylactic mastectomy (CPM) and determine whether survival differed for invasive breast cancer patients based on hormone ...receptor (HR) status and age.
METHODS:We identified women diagnosed with unilateral stage I to III breast cancer between 1998 and 2012 within the Surveillance, Epidemiology, and End Results registry. We compared characteristics and temporal trends between patients undergoing breast-conserving surgery, unilateral mastectomy, and CPM. We then performed Cox proportional-hazards regression to examine breast cancer-specific survival (BCSS) and overall survival (OS) in women diagnosed between 1998 and 2007, who underwent breast-conserving surgery with radiation (breast-conserving therapy), unilateral mastectomy, or CPM, with subsequent subgroup analysis stratifying by age and HR status.
RESULTS:Of 496,488 women diagnosed with unilateral invasive breast cancer, 59.6% underwent breast-conserving surgery, 33.4% underwent unilateral mastectomy, and 7.0% underwent CPM. Overall, the proportion of women undergoing CPM increased from 3.9% in 2002 to 12.7% in 2012 (P < 0.001). Reconstructive surgery was performed in 48.3% of CPM patients compared with only 16.0% of unilateral mastectomy patients, with rates of reconstruction with CPM rising from 35.3% in 2002 to 55.4% in 2012 (P < 0.001). When compared with breast-conserving therapy, we found no significant improvement in BCSS or OS for women undergoing CPM (BCSSHR 1.08, 95% confidence interval 1.01–1.16; OSHR 1.08, 95% confidence interval 1.03–1.14), regardless of HR status or age.
CONCLUSIONS:The use of CPM more than tripled during the study period despite evidence suggesting no survival benefit over breast conservation. Further examination on how to optimally counsel women about surgical options is warranted.
Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer.
Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated ...with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated.
In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively (
< .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity (
< .01).
The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.
Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib ...monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts.
Patients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m
twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression.
Forty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B).
Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted.
Purpose To estimate the contribution of differences in demographics, comorbidity, insurance, tumor characteristics, and treatment to the overall mortality disparity between nonelderly black and white ...women diagnosed with early-stage breast cancer. Patients and Methods Excess relative risk of all-cause death in black versus white women diagnosed with stage I to III breast cancer, expressed as a percentage and stratified by hormone receptor status for each variable (demographics, comorbidity, insurance, tumor characteristics, and treatment) in sequentially, propensity-scored, optimally matched patients by using multivariable hazard ratios (HRs). Results We identified 563,497 white and black women 18 to 64 years of age diagnosed with stage I to III breast cancer from 2004 to 2013 in the National Cancer Data Base. Among women with hormone receptor-positive disease, who represented 78.5% of all patients, the HR for death in black versus white women in the demographics-matched model was 2.05 (95% CI, 1.94 to 2.17). The HR decreased to 1.93 (95% CI, 1.83 to 2.04), 1.54 (95% CI, 1.47 to 1.62), 1.30 (95% CI, 1.24 to 1.36), and 1.25 (95% CI, 1.19 to 1.31) when sequentially matched for comorbidity, insurance, tumor characteristics, and treatment, respectively. These factors combined accounted for 76.3% of the total excess risk of death in black patients; insurance accounted for 37.0% of the total excess, followed by tumor characteristics (23.2%), comorbidities (11.3%), and treatment (4.8%). Results generally were similar among women with hormone receptor-negative disease, although the HRs were substantially smaller. Conclusion Matching by insurance explained one third of the excess risk of death among nonelderly black versus white women diagnosed with early-stage breast cancer; matching by tumor characteristics explained approximately one fifth of the excess risk. Efforts to focus on equalization of access to care could substantially reduce ethnic/racial disparities in overall survival among nonelderly women diagnosed with breast cancer.
IMPORTANCE: The use of contralateral prophylactic mastectomies (CPMs) among patients with invasive unilateral breast cancer has increased substantially during the past decade in the United States ...despite the lack of evidence for survival benefit. However, whether this trend varies by state or whether it is correlated with changes in proportions of reconstructive surgery among these patients is unclear. OBJECTIVE: To determine state variation in the temporal trend and in the proportion of CPMs among women with early-stage unilateral breast cancer treated with surgery. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 1.2 million women 20 years of age or older diagnosed with invasive unilateral early-stage breast cancer and treated with surgery from January 1, 2004, through December 31, 2012, in 45 states and the District of Columbia as compiled by the North American Association of Central Cancer Registries. Data analysis was performed from August 1, 2015, to August 31, 2016. EXPOSURE: Contralateral prophylactic mastectomy. MAIN OUTCOMES AND MEASURES: Temporal changes in the proportion of CPMs among women with early-stage unilateral breast cancer treated with surgery by age and state, overall and in relation to changes in the proportions of those who underwent reconstructive surgery. RESULTS: Among the 1 224 947 women with early-stage breast cancer treated with surgery, the proportion who underwent a CPM nationally increased between 2004 and 2012 from 3.6% (4013 of 113 001) to 10.4% (12 890 of 124 231) for those 45 years or older and from 10.5% (1879 of 17 862) to 33.3% (5237 of 15 745) for those aged 20 to 44 years. The increase was evident in all states, although the magnitude of the increase varied substantially across states. For example, among women 20 to 44 years of age, the proportion who underwent a CPM from 2004-2006 to 2010-2012 increased from 14.9% (317 of 2121) to 24.8% (436 of 1755) (prevalence ratio PR, 1.66; 95% CI, 1.46-1.89) in New Jersey compared with an increase from 9.8% (162 of 1657) to 32.2% (495 of 1538) (PR, 3.29; 95% CI, 2.80-3.88) in Virginia. In this age group, CPM proportions for the period from 2010 to 2012 were over 42% in the contiguous states of Nebraska, Missouri, Colorado, Iowa, and South Dakota. From 2004 to 2012, the proportion of reconstructive surgical procedures among women aged 20 to 44 years who were diagnosed with early-stage breast cancer and received a CPM increased in many states; however, it did not correlate with the proportion of women who received a CPM. CONCLUSIONS AND RELEVANCE: The increase in the proportion of CPMs among women with early-stage unilateral breast cancer treated with surgery varied substantially across states. Notably, in 5 contiguous Midwest states, nearly half of young women with invasive early-stage breast cancer underwent a CPM from 2010 to 2012. Future studies should examine the reasons for the geographic variation and increasing trend in the use of CPMs.
Objectives
To analyze self‐reported changes in physical function in older women with breast cancer receiving adjuvant chemotherapy.
Design
Secondary analysis of the Cancer and Leukemia Group B ...(CALGB) 49907 prospective randomized clinical trial.
Setting
CALGB institutions in the United States.
Participants
Women aged 65 and older with Stage I to III breast cancer enrolled in CALGB 49907 who had physical function data from before and after receipt of adjuvant chemotherapy (N=256; mean age 71.5, range 65–85).
Measurements
Participants were administered the physical function subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire before chemotherapy, at the end of chemotherapy, and 12 months after chemotherapy initiation. Functional decline was defined as a more than 10‐point decrease from baseline at each time point. Resilience was defined as return to within 10 points of baseline. Multivariable regression was used to examine pretreatment characteristics associated with physical function changes.
Results
Of 42% of participants who had physical function decline from before to the end of chemotherapy, 47% recovered by 12 months (were resilient). Almost one‐third experienced functional decline from before chemotherapy to 12 months later. Pretreatment fatigue was a risk factor for functional decline from before to the end of chemotherapy (P=.02). Risk factors for functional decline at 12 months included pretreatment dyspnea (P=.007) and being unmarried (P=.01).
Conclusion
Functional decline was common in older women receiving adjuvant chemotherapy for breast cancer in a clinical trial. Although half recovered their physical function, one‐third had a clinically meaningful decline at 12 months. Strategies are needed to prevent functional decline in older adults receiving chemotherapy. J Am Geriatr Soc 67:920–927, 2019.
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