Relationship Between Long Durations and Different Regimens of Hormone Therapy and Risk of Breast Cancer

Abstract

Context Women using combined estrogen and progestin hormone replacement therapy (CHRT) have an increased risk of breast cancer; however, data on use for long durations and on risk associated with patterns of use are lacking.Objective To evaluate relationships between durations and patterns of CHRT use and risk of breast cancer by histological type and hormone receptor status.Design Population-based case-control study.Setting Three counties in western Washington State.Participants Nine hundred seventy-five women 65-79 years of age diagnosed with invasive breast cancer from April 1, 1997, through May 31, 1999 lobular cases, 656 ductal cases, 114 cases with other histological type, and 9 cases with an unspecified histological type; estrogen receptor (ER)/progesterone receptor (PR) status: 646 ER+/PR+ cases, 147 ER+/PR− cases, and 101 ER−/PR− cases [6 ER−/PR+ cases and 75 cases with unknown ER/PR status were not included in the analyses herein]) and 1007 population controls. Main Outcome MeasuresRisks of invasive lobular, ductal, ER+/PR+, ER+/PR−, and ER−/PR− breast carcinomas. ResultsWomen using unopposed estrogen replacement therapy (ERT) (exclusive ERT use), even for 25 years or longer, had no appreciable increase in risk of breast cancer, although the associated odds ratios were not inconsistent with a possible small effect. Ever users of CHRT (includes CHRT users who also had used ERT) had a 1.7-fold (95% confidence interval [CI], 1.3-2.2) increased risk of breast cancer, including a 2.7-fold (95% CI, 1.7-4.3) increased risk of invasive lobular carcinoma, a 1.5-fold (95% CI, 1.1-2.0) increased risk of invasive ductal carcinoma, and a 2.0-fold (95% CI, 1.5-2.7) increased risk of ER+/PR+ breast cancers. The increase in risk was greatest in those using CHRT for longer durations (users for 5-14.9 years and Ն15 years had 1.5-fold [95% CI, 1.0-2.3] and 1.6-fold [95% CI, 1.0-2.6] increases in risk of invasive ductal carcinoma, respectively, and 3.7-fold [95% CI, 2.0-6.6] and 2.6-fold [95% CI, 1.3-5.3] increases in risk of invasive lobular carcinoma, respectively. Associations of similar magnitudes were seen among users of both sequential and continuous CHRT. Risks of ER+/PR− and ER−/ PR− tumors were not increased by use of any form of hormone replacement therapy; however, small numbers of these tumors limited power to detect possible associations.Conclusion These data suggest that use of CHRT is associated with an increased risk of breast cancer, particularly invasive lobular tumors, whether the progestin component was taken in a sequential or in a continuous manner.

Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma

“…Furthermore, our study demonstrated that most ILCs are characterized by a generally low proliferative index and high ER, PR and AR expression. This steroid receptor pattern clearly suggests a hormonal involvement in the pathogenesis of ILCs [10,23,24,38].…”

Changing pattern of age-specific breast cancer incidence in the Swiss canton of Geneva

“…The association with HRT use is stronger for lobular carcinoma than for ductal carcinoma [17,18]. In Belgium, Vankrunkelsven et al [7] found a larger decline in invasive lobular than in ductal carcinomas, while inverse results were found in the USA [19].…”

Les progr�s dans la lutte contre le cancer en France et dans l?Union europ�enne

“…Ce résultat pourrait sembler encourageant car pendant cette période l'incidence de ce cancer a nettement augmenté passant de 56 pour 100 000 en 1980 à 63 en 1985 et 89 en 2000 [68] soit 58 % après correction pour vieillissement de la population. Il est difficile de distinguer dans cette évolution ce qui revient aux différents facteurs possibles : accroissement du nombre des cas en raison du surdiagnostic (conséquence du dépis-tage), augmentation réelle due à l'exposition aux oestrogènes (puberté plus précoce, âge au premier enfant de 3 ans plus tardif), accroissement de l'indice de masse corporelle, la fréquence des cancers après la ménopause étant influencée par ce facteur [11,45,46,64,75], augmentation de la consommation d'alcool chez les femmes [75] et enfin plus grand usage des traitements hormonaux substitutifs, ce qui augmente la fréquence des cancers du sein [10,22,34,35,56,86] et réduit leur détectabilité par mammographie [28,36,48]. Il est donc devenu nécessaire de mettre en balance les avantages et les inconvénients de ces traitements substitutifs et de limiter leur durée et leurs indications [72].…”