Breastfeeding, PAM50 tumor subtype, and breast cancer prognosis and survival.
BACKGROUND
Breastfeeding is associated with decreased breast cancer risk, yet associations with prognosis and survival by tumor subtype are largely unknown.


METHODS
We conducted a cohort study of 1636 women from two prospective breast cancer cohorts. Intrinsic tumor subtype (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2]-enriched, basal-like) was determined by the PAM50 gene expression assay. Breastfeeding history was obtained from participant questionnaires. Questionnaires and medical record reviews documented 383 recurrences and 290 breast cancer deaths during a median follow-up of nine years. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between breastfeeding and tumor subtype. Cox regression was used to estimate hazard ratios (HRs) for breast cancer recurrence or death. Statistical significance tests were two-sided.


RESULTS
Breast cancer patients with basal-like tumors were less likely to have previously breastfed than those with luminal A tumors (OR = 0.56, 95% CI = 0.39 to 0.80). Among all patients, ever breastfeeding was associated with decreased risk of recurrence (HR = 0.70, 95% CI = 0.53 to 0.93), especially breastfeeding for six months or more (HR = 0.63, 95% CI = 0.46 to 0.87, P trend = .01). Similar associations were observed for breast cancer death. Among women with luminal A subtype, ever breastfeeding was associated with decreased risks of recurrence (HR = 0.52, 95% CI = 0.31 to 0.89) and breast cancer death (HR = 0.52, 95% CI = 0.29 to 0.93), yet no statistically significant associations were observed among the other subtypes. Effects appeared to be limited to tumors with lower expression of proliferation genes.


CONCLUSIONS
History of breastfeeding might affect prognosis and survival by establishing a luminal tumor environment with lower proliferative activity.
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML). marilyn.l.kwan@kp.org.
Marilyn L
ML
Kwan
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Philip S
PS
Bernard
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Candyce H
CH
Kroenke
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Rachel E
RE
Factor
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Laurel A
LA
Habel
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Erin K
EK
Weltzien
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Adrienne
A
Castillo
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Erica P
EP
Gunderson
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Kaylynn S
KS
Maxfield
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Inge J
IJ
Stijleman
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Bryan M
BM
Langholz
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Charles P
CP
Quesenberry
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Lawrence H
LH
Kushi
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Carol
C
Sweeney
Division of Research, Kaiser Permanente Northern California, Oakland, CA (MLK, CHK, LAH, EKW, AC, EPG, CPQJr, LHK, BJC); Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (PSB, REF, IJS, CS); Associated Regional and University Pathologist Institute for Clinical and Experimental Pathology, Salt Lake City, UT (PSB, REF); Division of Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT (KSM, CS); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (BML).
Bette J
BJ
Caan
D000328:Adult; D000368:Aged; D001942:Breast Feeding; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires