Age-related lobular involution and risk of breast cancer.
BACKGROUND
As women age, the lobules in their breasts undergo involution or regression. We investigated whether lobular involution in women with benign breast disease was associated with subsequent breast cancer risk.


METHODS
We examined biopsy specimens of 8736 women in the Mayo Benign Breast Disease Cohort from whom biopsy samples were taken between January 1, 1967, and December 31, 1991. Median follow-up for breast cancer outcomes was 17 years. We classified lobular involution in the background breast tissue as none (0% involuted lobules), partial (1%-74%), or complete (> or = 75%). Subsequent breast cancer events and data on other risk factors were obtained from medical records and follow-up questionnaires. To estimate relative risks (RRs), standardized incidence ratios were calculated by use of incidence rates from the Iowa Surveillance, Epidemiology, and End Results (SEER) Registry. All statistical tests were two-sided.


RESULTS
Distribution of extent of involution was none among 1627 (18.6%) women, partial among 5197 (59.5%), and complete among 1912 (21.9%). Increased involution was positively associated with increased age and inversely associated with parity (both P<.001). The relative risk for the entire cohort of 8736 women, compared with the Iowa SEER population, was 1.40 (95% CI = 1.30 to 1.51). Risk of breast cancer was associated with the extent of involution (for no involution, RR [i.e., observed versus expected] = 1.88, 95% confidence interval [CI] = 1.59 to 2.21; for partial involution, RR = 1.47, 95% CI = 1.33 to 1.61; and for complete involution, RR = 0.91, 95% CI = 0.75 to 1.10; test for heterogeneity P<.001). Lobular involution modified risk in all subsets (e.g., among women with atypia, for no involution, RR = 7.79, 95% CI = 3.56 to 14.81; for partial involution, RR = 4.06, 95% CI = 3.03 to 5.33; and for complete involution, RR = 1.49, 95% CI = 0.41 to 3.82; P = .003).


CONCLUSIONS
In this large cohort of women with benign breast disease, lobular involution was associated with reduced risk of breast cancer. Aberrant involution may be a biologically important phenomenon in breast cancer biology.
Milanese
Tia R
TR
Mayo Medical School, Rochester, MN 55905, USA.
Hartmann
Lynn C
LC
Sellers
Thomas A
TA
Frost
Marlene H
MH
Vierkant
Robert A
RA
Maloney
Shaun D
SD
Pankratz
V Shane
VS
Degnim
Amy C
AC
Vachon
Celine M
CM
Reynolds
Carol A
CA
Thompson
Romayne A
RA
Melton
L Joseph
LJ
Goode
Ellen L
EL
Visscher
Daniel W
DW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001706:Biopsy; D001940:Breast / Q000033:anatomy & histology / Q000502:physiology*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018275:Carcinoma, Lobular / Q000453:epidemiology / Q000517:prevention & control; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007484:Iowa / Q000453:epidemiology; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program