Sarcopenia (low muscle mass), poor muscle quality (low muscle radiodensity), and excess adiposity derived from computed tomography (CT) has been related to higher mortality in patients with ...metastatic breast cancer, but the association with prognosis in patients with nonmetastatic breast cancer is unknown.
To evaluate associations of all 3 body composition measures, derived from clinically acquired CT at diagnosis, with overall mortality in nonmetastatic breast cancer.
This observational study included 3241 women from Kaiser Permanente of Northern California and Dana Farber Cancer Institute diagnosed from January 2000 to December 2013 with stages II or III breast cancer. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with sarcopenia, low muscle radiodensity, and total adipose tissue (TAT). Models were adjusted for sociodemographics, tumor characteristics, treatment, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and other body composition measures. We also evaluated the cross-classification of categories of sarcopenia (yes/no) and tertiles of TAT, with outcomes.
Overall survival time and all-cause mortality.
Median (range) age of 3241 women included in this study was 54 (18-80) years, and median follow-up was 6.0 years; 1086 patients (34%) presented with sarcopenia, and 1199 patients (37%) had low muscle radiodensity. Among patients with nonmetastatic breast cancer, those with sarcopenia showed higher overall mortality (HR, 1.41; 95% CI, 1.18-1.69) compared with those without sarcopenia. Patients in the highest tertile of TAT also showed higher overall mortality (HR, 1.35; 95% CI, 1.08-1.69) compared with those in the lowest tertile. Low radiodensity was not associated with survival. In analyses of sarcopenia and TAT, highest mortality was seen in patients with sarcopenia and high TAT (HR, 1.89; 95% CI, 1.30-2.73); BMI alone was not significantly related to overall mortality and did not appropriately identify patients at risk of death owing to their body composition.
Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes.
Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival.
Muscle and adiposity at colorectal cancer diagnosis and survival were ...examined in a retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer-specific mortality (CRCsM).
Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% HR, 1.27; 95% confidence interval (CI), 1.09-1.48 higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and <30 kg/m
, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity.
Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker.
Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases.
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The 2008 Physical Activity (PA) Guidelines recommend engaging in at least 2.5 h (10 MET-hours/week) of moderate intensity PA per week (defined as 4 METs) to reduce risk of morbidity and mortality. ...This analysis was conducted to investigate whether this recommendation can be extended to breast cancer survivors. Data from four studies of breast cancer survivors measuring recreational PA from semi-quantitative questionnaires a median of 23 months post-diagnosis (interquartile range 18–32 months) were pooled in the After Breast Cancer Pooling Project (
n
= 13,302). Delayed entry Cox proportional hazards models were applied in data analysis with adjustment for age, post-diagnosis body mass index, race/ethnicity, menopausal status, TNM stage, cancer treatment, and smoking history. Engaging in at least 10 MET-hours/week of PA was associated with a 27% reduction in all-cause mortality (
n
= 1,468 events, Hazard Ratio (HR) = 0.73, 95% CI, 0.66–0.82) and a 25% reduction in breast cancer mortality (
n
= 971 events, HR = 0.75, 95% CI 0.65–0.85) compared with women who did not meet the PA Guidelines (<10 MET-hours/week). Risk of breast cancer recurrence (
n
= 1,421 events) was not associated with meeting the PA Guidelines (HR = 0.96, 95% CI, 0.86–1.06). These data suggest that adhering to the PA guidelines may be an important intervention target for reducing mortality among breast cancer survivors.
Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups.
We studied a diverse cohort of women with breast cancer from the Life ...After Cancer Epidemiology and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier.
In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, P Trend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 95% confidence intervals (CI), 2.3-8.4, whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3-0.9).
Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes.
Subtyping in a population-based cohort revealed distinct profiles by age and race.
The PAM50, a gene expression assay to categorize breast tumors into intrinsic subtypes, has not been previously used to examine short- and long-term prognostication in a population-based cohort where ...treatment patterns and time of initial follow-up vary.
In a stratified case-cohort design of 1,691 women from the LACE and Pathways breast cancer survivor cohorts, we used PAM50 to categorize tumors into Luminal A (LumA), Luminal B (LumB), HER2-enriched (HER2-E), Basal-like and Normal-like, and to examine risk of early and late recurrence and mortality by Cox proportional hazards regression.
Compared with LumA, cumulative risk of recurrence and breast cancer death was higher for LumB, HER2-E, and Basal-like tumors at 2, 5, and 10 years. However, HR of breast cancer death varied over time <5 years (early) vs. > 5 years (late) for both Basal-like (HR, 6.23 early vs. HR, 0.63 late) and HER2-E tumors (HR, 2.97 early vs. HR, 0.73 late) but not for LumB tumors where risk was elevated consistently (HR, 2.67 early vs. HR, 1.47 late). The contrast between LumB, HER2-E, and Basal-like compared with LumA on early recurrence was stronger when subtype was defined by PAM50 than by immunohistochemistry (IHC) markers.
The PAM50 categorized intrinsic subtypes in a manner that more accurately predicts recurrence and survival, especially for luminal tumors, compared with commonly used methods that rely on traditional IHC clinical markers.
The PAM50 is robust for use in epidemiologic studies and should be considered when archived tumor tissues are available.
There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer-related pharmaceutical ...exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort (women with early stage BC from the Kaiser Permanente Northern California Cancer Registry) to examine the association between beta blockers (BBs) and/or angiotensin-converting enzyme inhibitors (ACEi) and BC recurrence, BC-specific mortality, and overall mortality. Among 1,779 women, there were 292 BC recurrences, 174 BC deaths, and 323 total deaths. 23% were exposed to either a BB and/or an ACEi. These drugs were associated with older age, postmenopausal status, tamoxifen therapy, greater pre-diagnosis BMI, hypertension, and diabetes. In Cox proportional hazards models, ACEi exposure was associated with BC recurrence (HR 1.56, 95% CI 1.02, 2.39,
P
= 0.04), but not cause-specific or overall mortality. Combined ACEi and BB were associated with overall mortality (HR 1.94, 95% CI 1.22, 3.10,
P
= 0.01). BB exposure was associated with lower hazard of recurrence and cause-specific mortality. However, there was no evidence of a dose response with either medication. For recurrence and cause-specific mortality, BB combined with ACEi was associated with a lower HR for the outcome than when ACEi alone was used. These hypothesis generating findings suggest that BC recurrence and survival were associated with exposure to two commonly used classes of anti-hypertensive medications. These observations need to be confirmed and suggest that greater attention should focus on the potential role of these commonly used medications in BC outcomes.
To examine the association of alcohol consumption after breast cancer diagnosis with recurrence and mortality among early-stage breast cancer survivors.
Patients included 1,897 LACE study ...participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years postdiagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry. Alcohol consumption (ie, wine, beer, and liquor) was assessed at cohort entry using a food frequency questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% CI with adjustment for known prognostic factors.
Two hundred ninety-three breast cancer recurrences and 273 overall deaths were ascertained after an average follow-up of 7.4 years. Nine hundred fifty-eight women (51%) were considered drinkers (> 0.5 g/d of alcohol), and the majority drank wine (89%). Drinking ≥ 6 g/d of alcohol compared with no drinking was associated with an increased risk of breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83) and death due to breast cancer (HR, 1.51; 95% CI, 1.00 to 2.29). The increased risk of recurrence appeared to be greater among postmenopausal (HR, 1.51; 95% CI, 1.05 to 2.19) and overweight and obese women (HR, 1.60; 95% CI, 1.08 to 2.38). Alcohol intake was not associated with all-cause death and possibly associated with decreased risk of non-breast cancer death.
Consuming three to four alcoholic drinks or more per week after a breast cancer diagnosis may increase risk of breast cancer recurrence, particularly among postmenopausal and overweight/obese women, yet the cardioprotective effects of alcohol on non-breast cancer death were suggested.
Background
Although the proportion of triple‐negative breast cancers (TNBCs) diagnosed among older women is low, the number of TNBC cases is substantial because of the high incidence of breast cancer ...after the age of 65 years. The molecular features of TNBC in this age group have not been well described.
Methods
This study examined a population‐based cohort of women with stage I to III TNBC diagnosed between the ages of 25 and 91 years with the PAM50 gene expression subtyping assay. The concordance between the TNBC classification by immunohistochemistry and the gene expression classification by PAM50, the expression of individual genes, and 5‐year recurrence and breast cancer mortality in older women (≥65 years old) and younger women (<50 years old) was assessed.
Results
The molecular subtype distribution in TNBC was significantly different according to the age at diagnosis. TNBC was more likely to be classified as basal‐like in women younger than 50 years (sensitivity, 0.91; 95% confidence interval, 0.77‐0.97) than women 65 years old or older (sensitivity, 0.72; 95% confidence interval, 0.48‐0.87); 35% of clinical TNBC cases in the latter group were the human epidermal growth factor receptor 2 (HER2)–enriched subtype by molecular classification. Older women with TNBC also had significantly higher expression of ERBB2 and lower expression of all 10 proliferation‐associated genes tested (P < .01). The risk of breast cancer death within 5 years was significantly higher in women with TNBC in comparison with women with hormone receptor–positive cancers in all age groups.
Conclusions
This study revealed differences in molecular subtypes among clinical TNBC cases based on patient age. A potentially targetable HER2‐enriched group raises the possible need for intrinsic subtyping in older women with TNBC.
Triple‐negative breast cancers have different molecular subtypes among older women in comparison with younger women. A potentially targetable human epidermal growth factor receptor 2–enriched subtype is more common among women older than 65 years.
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