The aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer ...studies within a large health maintenance organization.
Tumor data on 2544 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) status were obtained (1868 luminal A tumors, 294 luminal B tumors, 288 triple-negative tumors and 94 Her2-overexpressing tumors). Demographic, reproductive and lifestyle information was collected either in person or by mailed questionnaires. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis, race/ethnicity, and study origin.
Compared with luminal A cases, luminal B cases were more likely to be younger at diagnosis (P = 0.0001) and were less likely to consume alcohol (OR = 0.74, 95% CI = 0.56 to 0.98), use hormone replacement therapy (HRT) (OR = 0.66, 95% CI = 0.46 to 0.94), and oral contraceptives (OR = 0.73, 95% CI = 0.55 to 0.96). Compared with luminal A cases, triple-negative cases tended to be younger at diagnosis (P < or = 0.0001) and African American (OR = 3.14, 95% CI = 2.12 to 4.16), were more likely to have not breastfed if they had parity greater than or equal to three (OR = 1.68, 95% CI = 1.00 to 2.81), and were more likely to be overweight (OR = 1.82, 95% CI = 1.03 to 3.24) or obese (OR = 1.97, 95% CI = 1.03 to 3.77) if premenopausal. Her2-overexpressing cases were more likely to be younger at diagnosis (P = 0.03) and Hispanic (OR = 2.19, 95% CI = 1.16 to 4.13) or Asian (OR = 2.02, 95% CI = 1.05 to 3.88), and less likely to use HRT (OR = 0.45, 95% CI = 0.26 to 0.79).
These observations suggest that investigators should consider tumor heterogeneity in associations with traditional breast cancer risk factors. Important modifiable lifestyle factors that may be related to the development of a specific tumor subtype, but not all subtypes, include obesity, breastfeeding, and alcohol consumption. Future work that will further categorize triple-negative cases into basal and non-basal tumors may help to elucidate these associations further.
BACKGROUND:Prepectoral breast reconstruction is increasingly popular. This study compares complications between 2 subpectoral and 1 prepectoral breast reconstruction technique.
METHODS:Between 2008 ...and 2015, 294 two-staged expander breast reconstructions in 213 patients were performed with 1 of 3 surgical techniques(1) Prepectoral, (2) subpectoral with acellular dermal matrix (ADM) sling (“Classic”), or (3) subpectoral/subserratus expander placement without ADM (“No ADM”). Demographics, comorbidities, radiation therapy, and chemotherapy were assessed for correlation with Clavien IIIb score outcomes. Follow-up was a minimum of 6 months.
RESULTS:Surgical cohorts (n = 165 Prepectoral; n = 77 Classic; n = 52 No ADM) had comparable demographics except Classic had more cardiac disease (P = 0.03), No ADM had higher body mass index (BMI) (P = 0.01), and the Prepectoral group had more nipple-sparing mastectomies (P < 0.001). Univariate analysis showed higher expander complications with BMI ≥ 40 (P = 0.05), stage 4 breast cancer (P = 0.01), and contralateral prophylactic mastectomy (P = 0.1), whereas implant complications were associated with prior history of radiation (P < 0.01). There was more skin necrosis (P = 0.05) and overall expander complications (P = 0.01) in the Classic cohort, whereas the No ADM group trended toward the lowest expander complications among the 3. Multivariate analysis showed no difference in overall expander complication rates between the 3 groups matching demographics, mastectomy surgery, risks, and surgical technique.
CONCLUSIONS:Prepectoral and subpectoral Classic and No ADM breast reconstructions demonstrated comparable grade IIIb Clavien score complications. BMI > 40, stage 4 cancer, and contralateral prophylactic mastectomy were associated with adverse expander outcomes and a prior history of radiation therapy adversely impacted implant outcomes. Ninety-day follow-up for expander and implant complications may be a better National Surgical Quality Improvement Program measure.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Objective With 2.3 million breast cancer survivors in the US today, identification of modifiable factors associated with breast cancer recurrence and survival is increasingly important. Only recently ...new studies have been designed to examine the impact of lifestyle factors on prognosis, including Pathways, a prospective study of women with breast cancer in Kaiser Permanente Northern California (KPNC). Methods Pathways aims to examine the effect on recurrence and survival of (1) lifestyle factors such as diet, physical activity, quality of life, and use of alternative therapies and (2) molecular factors such as genetic polymorphisms involved in metabolism of chemotherapeutic agents. Eligibility includes any woman diagnosed with invasive breast cancer within KPNC, no previous diagnosis of other invasive cancer, age 21 years or older, and ability to speak English, Spanish, Cantonese, or Mandarin. Newly diagnosed patients are identified daily from electronic pathology records and are enrolled within two months of diagnosis. An extensive baseline interview is conducted, blood and saliva samples are collected, and body measurements are taken. Women are followed for lifestyle updates, treatment, and outcomes by self-report and query of KPNC databases. Results Recruitment began in 9 January, 2006, and as of 16 January, 2008, 1,539 women have been enrolled along with collection of 1,323 blood samples (86%) and 1,398 saliva samples (91%). Conclusions The Pathways Study will become a rich resource to examine behavioral and molecular factors and breast cancer prognosis.
Breast cancer-related lymphedema (BCRL) is a serious chronic condition after breast cancer (BC) surgery and treatment. It is unclear if BCRL risk varies by race/ethnicity. In a multiethnic ...prospective cohort study of 2953 BC patients, we examined the association of self-reported BCRL status with self-reported race/ethnicity and estimated genetic ancestry. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated by multivariable Cox proportional hazards models, with follow-up starting 6 months post-BC diagnosis. Estimates were further stratified by body mass index (BMI). By 48 months of follow-up, 342 (11.6 %) women reported having BCRL. Younger age at BC diagnosis, higher BMI at baseline, and lower physical activity were associated with greater BCRL risk. African American (AA) women had a 2-fold increased risk of BCRL compared with White women (HR = 2.04; 95 % CI 1.35–3.08). African genetic ancestry was also associated with an increased risk (HR = 2.50; 95 % CI 1.43, 4.36). Both risks were attenuated but remained elevated after adjusting for known risk factors and became more pronounced when restricted to the nonobese women (adjusted HR = 2.31 for AA and HR = 3.70 for African ancestry, both
p
< 0.05). There was also evidence of increased BCRL risk with Hispanic ethnicity in the nonobese women. Nonobese AA women had a higher risk of BCRL than White women, which cannot be fully explained by known risk factors. This is the first large-scale, prospective study demonstrating differences in BCRL risk according to race/ethnicity as assessed by both self-report and genetic ancestry data, with a potential ancestry–obesity interaction.
Breast cancer patients have voiced dissatisfaction regarding their education on breast cancer-related lymphedema risk and risk reduction strategies from their clinicians. Informing patients about ...lymphedema can contribute to decrease their risk of developing the condition, or among those already affected, prevent it from progressing further. In this cross-sectional study, a lymphedema awareness score was calculated based on responses to a brief telephone interview conducted among 389 women diagnosed with invasive breast cancer at Kaiser Permanente Northern California from 2000 to 2008 and had a previous record of a lymphedema-related diagnosis or procedure in their electronic medical record. During the telephone interview, women self-reported a lymphedema clinical diagnosis, lymphedema symptoms but no lymphedema diagnosis, or neither a diagnosis nor symptoms, and responded to questions on lymphedema education and support services as well as health knowledge. Multivariable logistic regression odds ratio (OR) and 95 % confidence interval (CI) was used to determine the associations of selected sociodemographic and clinical factors with the odds of having lymphedema awareness (adequate vs. inadequate). The median (range) of the lymphedema awareness score was 4 (0–7). Compared with patients <50 years of age, patients 70+ years of age at breast cancer diagnosis had lower odds of adequate lymphedema awareness (OR 0.25; 95 % CI 0.07, 0.89), while patients 50–59 and 60–69 years had greater odds of adequate awareness although not statistically significant (OR 2.05; 95 % CI 0.88, 4.78 and OR 1.55; 95 % CI 0.60, 4.02, respectively;
p
for trend = 0.09). Higher educational level and greater health literacy were suggestive of adequate awareness yet were not significant. These results can help inform educational interventions to strengthen patient knowledge of lymphedema risk and risk reduction practices, particularly in an integrated health care delivery setting. With the growing population of breast cancer survivors, increasing patient awareness and education about lymphedema risk reduction and care after cancer diagnosis is warranted.
Breast cancer survivors have reported dissatisfaction regarding their education on risk of breast cancer-related lymphedema (BCRL) from clinicians. We describe clinician knowledge and treatment ...referral of patients with BCRL among active oncologists, surgeons, and primary care physicians in the Kaiser Permanente Northern California Medical Care Program. A total of 887 oncologists, surgeons, and primary care clinicians completed a 10-minute web survey from May 2, 2010 to December 31, 2010 on BCRL knowledge, education, and referral patterns. A knowledge score of BCRL was calculated based on clinician responses. Multivariable regression models were used to determine the associations of selected covariates with BCRL knowledge score and clinician referral, respectively. Compared with primary care clinicians, oncologists had the highest mean score followed closely by surgeons (
P
< 0.0001). In multivariable analyses, being female, an oncologist or surgeon, and recently receiving BCRL materials were each significantly associated with higher BCRL knowledge scores. About 44% of clinicians (
n
= 381) indicated they had ever made a BCRL referral (100% oncologists, 79% surgeons, and 36% primary care clinicians). Clinicians with a higher knowledge score were more likely to make referrals. In stratified analyses by specialty, the significant associated factors remained for primary care but became non-significant for oncology and surgery. These results can inform educational interventions to strengthen clinician knowledge of the clinical management of BCRL, especially among primary care clinicians. With the growing number of breast cancer survivors, increasing clinician education about BCRL across all specialties is warranted.
OBJECTIVE To determine the incidence of breast cancer–related lymphedema (BCRL) during the early survivorship period as well as demographic, lifestyle, and clinical factors associated with BCRL ...development. DESIGN The Pathways Study, a prospective cohort study of breast cancer survivors with a mean follow-up time of 20.9 months. SETTING Kaiser Permanente Northern California medical care program. PARTICIPANTS We studied 997 women diagnosed from January 9, 2006, through October 15, 2007, with primary invasive breast cancer and who were at least 21 years of age at diagnosis, had no history of any cancer, and spoke English, Spanish, Cantonese, or Mandarin. MAIN OUTCOME MEASURE Clinical indication for BCRL as determined from outpatient or hospitalization diagnostic codes, outpatient procedural codes, and durable medical equipment orders. RESULTS A clinical indication for BCRL was found in 133 women (13.3%), with a mean time to diagnosis of 8.3 months (range, 0.7-27.3 months). Being African American (hazard ratio, 1.93; 95% confidence interval, 1.00-3.72) or more educated (P for trend = .03) was associated with an increased risk of BCRL. Removal of at least 1 lymph node (hazard ratio, 1.04; 95% confidence interval, 1.02-1.07) was associated with an increased risk, yet no significant association was observed for type of lymph node surgery. Being obese at breast cancer diagnosis was suggestive of an elevated risk (hazard ratio, 1.43; 95% confidence interval, 0.88-2.31). CONCLUSIONS In a large cohort study, BCRL occurs among a substantial proportion of early breast cancer survivors. Our findings agree with those of previous studies on the increased risk of BCRL with removal of lymph nodes and being obese, but they point to a differential risk according to race or ethnicity.Arch Surg. 2010;145(11):1055-1063-->
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Background: Kaiser Permanente (KP) is an integrated healthcare system providing comprehensive services to over 10 million members. The KP Interregional Breast Care Leaders, a ...multidisciplinary clinician group, developed a comprehensive evidence/consensus-based algorithm for breast cancer survivors, the KP Breast Cancer Survivorship National Clinical Algorithm (BCSNCA). The BCSNCA is intended to reduce variation in medical and psychosocial surveillance and improve outcomes by providing guidance to locally implemented survivorship programs, ie, recommendations for surveillance, late effects management, and risk reduction. As a quality improvement project, we evaluated regional/ facility level implementation. Methods: Qualitative data on BCSNCA implementation was collected from key informant interviews with oncology providers for 20 sites in 6 regions: Georgia, Colorado, Hawaii, Southern (KPSC) and Northern California (KPNC), and Mid-Atlantic, and by attending BCSNCA meetings. Implementation activities were recorded, categorized, and compared to BCSNCA. Results: Facilities in 3 regions implemented discrete BCSNCA components: Northwest and Georgia facilities implemented dedicated survivorship clinics; a KPSC facility piloted a nurse navigator standardized psychosocial assessment; KPNC implemented local guidelines, similar to the BCSNCA. One region has not implemented; Georgia implemented all BCSNCA components. There is variation within each region. Implementation drivers include available resources, competing QI priorities/leadership preferences, and adaptability of extant programs. Conclusions: We found variation between and within regions. The BCSNCA content accommodates variation in implementation, guided by a complex set of factors, including resource availability, leadership preferences, and local organizational goals. Even in integrated systems, the need for locally driven guideline adaptation is critical. Next step: assessment of BCSNCA components on patient-level outcomes.
Abstract
Background: Breast cancer-related lymphedema (BCRL) is a serious chronic condition that can occur in about 30% of patients after breast cancer (BC) surgery and treatment. Patient risk ...factors include younger age, higher BMI, and less physical activity. With few studies to date, it is largely unknown if BCRL risk varies by race/ethnicity.
Methods: In a prospective study of 2,953 BC patients, we examined the association of self-reported BCRL status at 12 and 48 months post-BC diagnosis with self-reported race/ethnicity and genetic ancestry. We also assessed associations with other clinical and patient factors. Race/ethnicity (White, African American (AA), Hispanic, Asian, and Other) was asked in the baseline interview at cohort entry. Genetic ancestry was estimated based on a validated panel of 124 ancestry informative markers (AIMs) using the STRUCTURE program. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by multivariable Cox proportional hazards models, with follow-up until date of BCRL self-report or last patient contact, whichever occurred first.
Results: 342 (11.6%) women reported having BCRL at 12 or 48 month follow-up, with 204 who were White, 37 AA, 41 Hispanic, 49 Asian, and 11 Other. Younger age at BC diagnosis, higher BMI at baseline, and less moderate-vigorous physical activity were associated with greater BCRL risk. After adjusting for sociodemographic and clinical factors, AA women had a significant 1.6-fold increased risk of BCRL (HR = 1.57; 95% CI: 1.09, 2.26) and Hispanic women had a borderline 1.4-fold increased risk (HR = 1.37; 95% CI: 0.99, 1.89), compared with White women. Consistent with self-reported race/ethnicity, African ancestry was associated with a 1.8-fold increased risk of BCRL (HR = 1.80; 95% CI: 1.15, 2.81). When the race/ethnicity and ancestry models were further adjusted for BCRL risk factors, i.e., age at BC diagnosis, BMI, and physical activity, associations became attenuated and non-significant among AA (HR = 1.26, 95% CI: 0.87-1.83) and Hispanic women (HR = 1.19, 95% CI: 0.85-1.68), and with African ancestry (HR = 1.38, 95% CI: 0.88-2.19). Results were similar when excluding BCRL events within 6 months of BC diagnosis to rule out transient post-operative swelling, except a suggestive increased risk of BCRL remained among AA women (HR = 1.47, 95% CI: 0.94-2.28) and with African ancestry (HR = 1.70, 95% CI: 0.99-2.91) after adjustment for BCRL risk factors. Further, the elevated BCRL risk seen in AA or Hispanic women, and with African ancestry, appeared to be stronger in non-obese compared with obese women.
Discussion: AA women had increased risk of BCRL compared with White women, which is partly attributed to differences in age at BC diagnosis, BMI, and physical activity. This is the first large-scale, prospective study to examine a racial/ethnic disparity of BCRL risk with self-report and genetic ancestry data.
Funded by R01 CA105274.
Citation Format: Marilyn L. Kwan, Valerie S. Lee, Janise M. Roh, Isaac J. Ergas, Yali Zhang, Susan E. Kutner, Charles P. Quesenberry, Christine B. Ambrosone, Lawrence H. Kushi, Song Yao. Race/ethnicity, genetic ancestry, and breast cancer-related lymphedema. abstract. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3724. doi:10.1158/1538-7445.AM2015-3724
Abstract
Background: With over 2.8 million breast cancer survivors in the U.S. today, there is increasing interest and need to identify factors associated with recurrence and survival. The Pathways ...Study was designed to examine the effects of lifestyle (e.g., diet, physical activity, complementary and alternative medicine CAM), psychosocial (e.g., quality of life), molecular and genetic, medical care, and contextual (e.g., social and built environment characteristics) factors on breast cancer prognosis.
Methods: Women newly-diagnosed with invasive breast cancer were identified daily from Kaiser Permanente Northern California (KPNC) electronic pathology records from January 2006 to April 2013; KPNC is a large, integrated health care organization. Eligibility included age at diagnosis of at least 21 y, no previous history of invasive cancer, and English, Spanish or Chinese-speaking. Women were enrolled during an in-person baseline interview that took place on average two months post-diagnosis, with collection of blood and saliva specimens. Active follow-up to update lifestyle and other factors and ascertain outcomes occurs periodically. Outcomes are also identified using KPNC electronic databases and confirmed via medical record review.
Results: The final study cohort consists of 4,505 women, with blood and saliva collected from 90% and 95% of participants, respectively. The cohort has substantial racial/ethnic diversity: 64.2% White, 12.4% Hispanic, 12.8% Asian, 7.9% African American, 2.7% other. The mean age at diagnosis was 59.6 y (range: 23.6-94.8 y). Educational attainment is high, with 84.1% of the cohort having at least some college education. Most women were diagnosed with AJCC Stage I (54.0%) or II (34.6%) cancers, and receptor status was positive for estrogen in 83% of women, progesterone in 63.4%, and Her2 in 12.3%.
As of December 1, 2013, 307 recurrences and 327 deaths have been confirmed, with 490 experiencing either. Initial age-adjusted results with proportional hazards regression demonstrate poorer disease-free survival (DFS) among African Americans (hazard ratio HR=1.84, 95% confidence interval CI,1.39-2.45) and better DFS among Asians (HR=0.70, 95% CI, 0.49, 1.00) compared to Whites. Greater stage at diagnosis, increasing age, and negative ER status are also associated with poorer DFS.
Discussion: The Pathways Study is a rich, unique resource collecting data on multiple factors that may influence breast cancer prognosis, including lifestyle, molecular, medical, and contextual factors. To date, 14 papers have been published on topics ranging from CAM use, quality of life, and physical activity during treatment, to tumor DNA methylation profiles and correlates of breast cancer molecular subtypes. With continued follow-up, it promises to provide findings on factors influencing prognosis to help guide breast cancer care.
Citation Format: Lawrence H. Kushi, Marilyn L. Kwan, Isaac J. Ergas, Cecile A. Laurent, Julie R. Munneke, Janise M. Roh, Heather Greenlee, Chi-Chen Hong, Theresa H. Keegan, Dawn L. Hershman, Susan E. Kutner, Marion M. Lee, Jeanne Mandelblatt, Alfred I. Neugut, Peggy Reynolds, Salma Shariff-Marco, Li Tang, Song Yao, Janice Barlow, Scarlett Lin Gomez, John K. Wiencke, Christine B. Ambrosone. A prospective study of breast cancer prognosis in Kaiser Permanente Northern California: Cohort description and initial findings from the Pathways Study. abstract. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4127. doi:10.1158/1538-7445.AM2014-4127
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