Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis

BACKGROUND: Little information is available on how the risk of breast cancer associated with the use of hormone therapy for menopause varies by histological type. We aimed to describe such associations for eight histological types of breast cancer. METHODS: Analyses are based on 1 031 224 postmenopausal women recruited in 1996-2001 into a nationwide UK cohort study, and followed for incident cancer and death. Relative risks associated with use of hormone therapy were estimated for eight histological types of breast cancer. FINDINGS: During 3.6 million person-years of follow-up, 14 102 breast cancers were diagnosed, of which 13 782 (98%) had histological type recorded: 11 869 (86%) were invasive, including 8007 ductal, 1526 lobular, 365 mixed ductal-lobular, 492 tubular, 71 medullary, and 148 mucinous cancers; and 1913 (14%) were in situ, including 1443 ductal and 86 lobular cancers. The relative risks of invasive breast cancer in current users compared with never users of hormone therapy varied significantly according to tumour histology overall (p<0.0001), for users of oestrogen-only therapy (p=0.0001), and for users of oestrogen-progestagen therapy (p<0.0001). The largest relative risks in current compared with never users of hormone therapy were seen for lobular (relative risk 2.25, 95% CI 2.00-2.52), mixed ductal-lobular (2.13, 1.68-2.70), and tubular cancers (2.66, 2.16-3.28). The relative risks for ductal and mucinous cancers were 1.63 (95% CI 1.55-1.72) and 1.58 (1.08-2.31), respectively. The risk of medullary cancer was not increased (0.74, 0.43-1.28). The relative risk of in-situ disease in current users compared with never users of hormone therapy also varied significantly according to histological type (p=0.03), with a relative risk for lobular carcinoma in situ of 2.82 (1.72-4.63) and 1.56 (1.38-1.75) for ductal carcinoma in situ. The effects of hormone therapy on invasive ductal, lobular, and tubular cancer were generally greater for oestrogen-progestagen therapy than for oestrogen-only therapy, and were attenuated with increasing body-mass index (BMI). INTERPRETATION: The risks associated with use of hormone therapy for menopause differ by histological type of breast cancer, and are substantially attenuated with increasing BMI.     

Postmenopausal hormone use and breast cancer associations differ by hormone regimen and histologic subtype

BACKGROUND:

Data from large prospective studies are needed to fully characterize the impact of exogenous hormones on breast cancer incidence by type of hormone preparation and histology of the cancer.

METHODS:

In a prospective cohort of 67,754 postmenopausal women in the US, 1821 cases of invasive ductal cancer and 471 cases of invasive lobular or mixed lobular cancer occurred during 13 years of follow‐up. The authors computed age‐adjusted rates, as well as age‐adjusted and multivariate‐adjusted rate ratios (RR) for ductal and lobular breast cancer and for the use of estrogen only (E‐only) and estrogen and progesterone (E + P) for current and former hormone users by duration of use and years since last use.

RESULTS:

Current use of E + P was associated with an increased risk of both ductal (RR of 1.75; 95% confidence interval [95% CI], 1.53‐2.01) and lobular (RR of 2.12; 95% CI, 1.62‐2.77) breast cancer. Risk increased within the first 2 to 3 years of use and attenuated 2 years after cessation. In contrast, current use of E‐only was not associated with an overall increased risk of invasive ductal cancer. The only exceptions to this finding were in lean (body mass index <25) women and for ductal cancers diagnosed at the regional/distant stage, where in both cases the use of E‐only was associated with an increased risk. E‐only use was associated with a 50% increased risk of invasive lobular cancer after ≥10 years of use.

CONCLUSIONS:

Use of E + P is more detrimental to the breast than E‐only use, in terms of both ductal and lobular cancer. The findings from the current study suggest a window of 2 to 3 years for the risks of E + P both to become apparent after initial use and to attenuate after cessation. Cancer 2009. © 2009 American Cancer Society.     

The relationship between alcohol use and risk of breast cancer by histology and hormone receptor status among women 65-79 years of age.

Alcohol consumption is associated with a moderate increase in breast cancer risk, possibly because alcohol increases estrogen levels in blood. Certain types of breast carcinomas are more hormonally responsive than others, including those that have a lobular histology or are hormone receptor positive, but few studies evaluating alcohol use and breast cancer risk have stratified results by histology or estrogen receptor (ER)/progesterone receptor (PR) status. We conducted a population-based case-control study of women 65-79 years of age in western Washington State. Women (975) diagnosed with invasive breast cancer during 1997-1999 were compared with 1007 controls. Ever-use of alcohol over the past 20 years was associated with a 1.3-fold [95% confidence interval (CI), 1.0-1.5] increased risk of breast cancer, although this increase was primarily limited to women who consumed > or =30.0 g/day of alcohol [odds ratio (OR), 1.7; 95% CI, 1.1-2.6]. Differences in risk by histology were observed: ever-use of alcohol was associated with a 1.8-fold (95% CI, 1.3-2.5) increased risk of lobular cancer but only a 1.2-fold (95% CI, 0.9-1.4) increased risk of ductal cancer. Ever-users of alcohol had an increase in risk of ER+/PR+ tumors (OR, 1.3; 95% CI, 1.1-1.7), but no change in their risks of ER+/PR- or ER-/PR- tumors. Alcohol use appears to be more strongly associated with risk of lobular carcinomas and hormone receptor-positive tumors than it is with other types of breast cancer. These results are consistent with there being an underlying hormonal basis for the known association between alcohol use and breast cancer incidence.     

Late age at first full term birth is strongly associated with lobular breast cancer

BACKGROUND:

Late age at first full‐term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades.

METHODS:

The purpose of this population‐based case‐control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer. Women with breast cancer were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control subjects were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ductal, lobular, and mixed ductal‐lobular breast cancer diagnosis in association with AFB and nulliparity.

RESULTS:

AFB ≥30 years was associated with a 2.4‐fold increase in risk of lobular breast cancer compared with AFB <20 years (OR, 2.4; 95% CI, 1.9‐2.9). The association was less pronounced for ductal breast cancer (OR, 1.3; 95% CI, 1.2‐1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared with women with AFB <20 years, but the association was stronger for lobular (OR, 1.7; 95% CI, 1.3‐2.2) than for ductal (OR, 1.2; 95% CI, 1.1‐1.3) subtypes (P = .004). The adverse effects of later AFB was stronger with obesity (P = .03) in lobular, but not ductal, breast cancer.

CONCLUSIONS:

Stronger associations observed for late AFB and nulliparity suggest that these factors preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer. Cancer 2011. © 2010 American Cancer Society.     

Relationship between established breast cancer risk factors and risk of seven different histologic types of invasive breast cancer.

BACKGROUND: Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types. METHODS: Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression. RESULTS: Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma. CONCLUSIONS: Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer.     

Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case-control study

Introduction

Breast cancers of different histology have different clinical and prognostic features. There are also indications of differences in aetiology. We therefore evaluated the risk of the three most common histological subtypes in relation to menopausal hormone therapy and other breast cancer risk factors.

Methods

We used a population-based case-control study of breast cancer to evaluate menopausal hormone therapy and other breast cancer risk factors for risk by histological subtype. Women aged 50 to 74 years, diagnosed with invasive ductal (n = 1,888), lobular (n = 308) or tubular (n = 93) breast cancer in Sweden in 1993 to 1995 were compared with 3,065 age-frequency matched controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ductal, lobular, and tubular cancer.

Results

Women who had used medium potency estrogen alone were at increased risks of both ductal and lobular cancer. Medium potency estrogen-progestin was associated with increased risks for all subtypes, but the estimates for lobular and tubular cancer were higher compared with ductal cancer. We found OR 5.6 (95% CI 3.2–9.7) for lobular cancer, OR 6.5 (95% CI 2.8–14.9) for tubular cancer and OR 2.3 (95% CI 1.6–3.3) for ductal cancer with ≥5 years use of medium potency estrogen-progestin therapy. Low potency oral estrogen (mainly estriol) appeared to be associated with an increased risk for lobular cancer, but the association was strongest for short-term use. Reproductive and anthropometric factors, smoking, and past use of oral contraceptives were mostly similarly related to the risks of the three breast cancer subtypes. Recent alcohol consumption of > 10 g alcohol/day was associated with increased risk only for tubular cancer (OR 3.1, 95% CI 1.4–6.8).

Conclusion

Menopausal hormone therapy was associated with increased risks for breast cancer of both ductal and lobular subtype, and medium potency estrogen-progestin therapy was more strongly associated with lobular compared with ductal cancer. We also found medium potency estrogen-progestin therapy and alcohol to be strongly associated with tubular cancer. With some exceptions, most other risk factors seemed to be similarly associated with the three subtypes of breast cancer.     

Relationship between histamine2-receptor antagonist medications and risk of invasive breast cancer

BACKGROUND: Histamine(2)-receptor antagonist (H(2) blocker) medications are used to treat heartburn, gastroesophageal reflux disease, and ulcers. Some H(2) blockers, specifically cimetidine and ranitidine, also increase serum prolactin concentrations. Given the positive relationship between prolactin levels and postmenopausal breast cancer risk, use of H(2) blockers is a potential breast cancer risk factor. The few previous studies evaluating this association have been null but have been limited by small sample sizes, and none have evaluated risk by either histologic type or estrogen receptor/progesterone receptor status. METHODS: Combining data from two population-based case-control studies conducted in western Washington, we assessed the relationship between use of H(2) blockers and risk of different types of breast cancer among 1,941 cases and 1,476 controls 55 to 79 years old. Odds ratios and 95% confidence intervals (95% CI) were calculated using polytomous logistic regression. RESULTS: Current use of H(2) blockers overall, cimetidine, and famotidine was not associated with an increased risk of either invasive ductal or invasive lobular breast cancer. Current users of ranitidine had a 2.2-fold (95% CI, 1.1-4.3) increased risk of ductal carcinoma that was confined to a 2.4-fold (95% CI, 1.2-4.9) increased risk of estrogen receptor-positive/progesterone receptor-positive ductal carcinoma. CONCLUSIONS: Use of H(2) blockers in general is not associated with an increased risk of breast cancer, although current use of ranitidine may increase risk of hormone receptor-positive ductal carcinoma. Further studies to confirm this finding are warranted.     

Invasive breast cancer following ductal and lobular carcinoma in situ of the breast

We considered the risk of subsequent invasive breast cancer in a population-based series of 579 carcinomas in situ (CIS) of the breast (482 ductal, 88 lobular) registered between 1977 and 2002 in the Swiss Canton of Vaud. A total of 55 cases of invasive breast cancer were observed vs. 12.3 expected, corresponding to a standardized incidence ratio (SIR) of 4.5 (95% confidence interval [CI], 3.4-5.8). The SIR was 4.6 after ductal and 4.2 after lobular CIS, was similar with passing time since CIS diagnosis, but was higher (SIR = 5.5) for women aged <55 years. At 20 years following CIS, the cumulative risk of invasive breast cancer was 26%, similar for lobular and for ductal CIS. The incidence of invasive breast cancer following CIS showed no consistent pattern of trends with age, all rates in subsequent age groups ranging between 10 and 18 in 1,000. This is compatible with the occurrence of a single mutational event in a population of susceptible women.     

The risk of breast cancer associated with specific patterns of migraine history

Purpose

Studies have suggested that a history of migraines may be associated with a lower risk of some types of breast cancer, though biological mechanisms are unclear. Identifying specific characteristics of migraines which are most strongly associated with breast cancer risk could improve our understanding of this relationship.

Methods

We ascertained specific characteristics of women’s migraine histories (severity, timing features, and presence of migraine aura). We used polytomous logistic regression to estimate the risk of ER+ ductal, ER? ductal, ER+ lobular, and ER+ ductal–lobular breast cancer associated with self-reported characteristics of migraine history. A total of 715 breast cancer cases (276 ER+ ductal, 46 ER? ductal, 191 ER+ lobular, and 202 ER+ ductal–lobular) and 376 controls ages 55–74 years were included in this population-based case–control study.

Results

Compared to women without a migraine history, women with a >30-year history of migraines had a 60 % (95 % CI 0.2–0.6) lower risk of ER+ ductal breast cancer; those who had their first migraine before age 20 had 50 % lower risks of ER+ ductal and ER+ lobular breast cancer (both 95 % CIs 0.3–0.9), and women who experienced migraine with aura had 30 % (95 % CI 0.5–0.98) and 40 % (95 % CI 0.4–0.9) lower risks of ER+ ductal and ER+ lobular breast cancer, respectively.

Conclusion

The lower risk of ER+ breast cancer associated with migraine appears to be limited to those women with early onset or long duration of migraine history, or those who experienced migraine with aura. This expands our understanding of the relationship between migraine and breast cancer and provides additional insight into potential underlying biological mechanisms.     

Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy

In a large population-based case-control study in Germany, including 3,464 breast cancer cases aged 50-74 at diagnosis and 6,657 population based and frequency matched controls, we investigated the effects of menopausal hormone therapy (HT) by type, regimen, timing and progestagenic constituent on postmenopausal breast cancer risk overall and according to histological type. Data were collected by face-to-face interviews. Logistic and polytomous logistic regression analysis were used to estimate odds ratios (OR) and 95%-confidence intervals (95% CI). Risk of invasive breast cancer was significantly elevated in current users (OR, 1.73, 95% CI, 1.55-1.94) and heterogeneous by histological type (p < 0.01), being more than 2-fold higher for lobular and tubular than for ductal cancer. Risks for current users varied significantly by type and regimen of HT, with ORs per year of use of 1.05 (95% CI, 1.04-1.06) for continuous combined estrogen-progestagen, 1.03 (95% CI, 1.02-1.04) for cyclical EP and 1.01 (95% CI, 1.00-1.03) for estrogen-only therapy. No statistically significant increase in risk was observed after 5 years of cessation of HT use for any histological type. Analyses of progestagenic content by regimen revealed a significantly higher risk for continuously administered norethisterone- or levonorgestrel-derived progestagens than for continuously administered progesterone-derived progestagens (OR, 2.27, 95% CI, 1.98-2.62 vs. 1.47, 95% CI, 1.12-1.93, respectively, p = 0.003), which may be explained by dose rather than type of progestagen. These data suggest that the risks associated with menopausal HT differ by type and regimen of HT and histological type of breast cancer and may vary by progestagenic component, depending on the effective dose.     

Progestagens use before menopause and breast cancer risk according to histology and hormone receptors

In a previous study, we found a positive association between premenopausal use of progestagens and breast cancer risk. We conducted the present study to assess the risk of breast cancers defined by their histology and hormone receptors status. We evaluated the association between progestagen-only intake (except for mini pills) before menopause and after the age of 40 years and invasive breast cancer risk in 67,057 women participating in the French E3N cohort study. Histologically confirmed invasive breast cancers (2,264) were identified through biennial self-administered questionnaires completed from 1992 to 2002. Risk estimates were calculated using the Cox proportional hazard model. We found an increased risk of lobular carcinoma associated with premenopausal use of progestagens among both current and past users [hazard ratio (HR), 1.51; 95% confidence interval (95% CI), 1.02-2.24 and HR, 1.38; 95% CI, 1.08-1.75, respectively]. Among current users, the use of progestagens for 4.5 years or more was associated with an increased risk of estrogen receptor-positive/progesterone receptor-positive carcinomas (HR, 1.68; 95% CI, 1.05-2.68), whereas current use of progestagens for <4.5 years was associated with an increase in the estrogen receptor-positive/progesterone receptor-negative carcinoma risk (HR, 1.61; 95% CI, 1.05-2.46). The premenopausal use of progestagens after the age of 40 years may be preferentially associated with the risk of lobular breast cancer and differentially affect the risk of breast cancer according to the hormone receptor status.     

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.     

Hormone replacement therapy in relation to risk of lobular and ductal breast carcinoma in middle-aged women

BACKGROUND: In the majority of studies, long term, recent use of hormone replacement therapy has been associated with an increased risk of breast carcinoma. However, little attention has been paid to the possibility that the magnitude of this association may vary according to the histologic type of breast carcinoma. METHODS: In this population-based case-control study, interviews were conducted with 537 female residents of King County, Washington who were ages 50-64 years and who had been diagnosed with primary breast carcinoma between January 1, 1988 and June 30, 1990. Interviews with 492 randomly selected King County women without a history of breast carcinoma served as a basis for comparison. Analyses were performed separately for women with lobular and for those with ductal tumors. RESULTS: Compared with nonusers of menopausal hormones, those who currently were using combined estrogen and progestin hormone replacement therapy (CHRT) and had done so for at least 6 months had an elevated risk of lobular breast carcinoma (odds ratio [OR] = 2.6; 95% confidence interval [95% CI], 1.1-5.8), but no change in their risk of ductal breast carcinoma was noted (OR = 0.7; 95% CI, 0.5-1. 1). The OR associated with current use of unopposed estrogen for at least 6 months was 1.5 (95% CI, 0.5-3.9) for lobular tumors and 0.7 (95% CI, 0.4-1.1) for ductal tumors. Similar results were found when cases of invasive tumor were analyzed separately. CONCLUSIONS: The results of this study suggest that CHRT use increases the risk of lobular, but not ductal, breast carcinoma in middle-aged women.     

The association between oral contraceptive use and lobular and ductal breast cancer in young women

Recent reports indicate that the incidence of lobular breast cancer is increasing at a faster rate than ductal breast cancer, which may be due to the differential effects of exogenous hormones by histology. To address this issue, we examined whether the relationship between oral contraceptive use and incident breast cancer differs between lobular and ductal subtypes in young women. A population-based sample of in situ and invasive breast cancer cases between ages 20 and 44 were recruited from Atlanta, GA; Seattle-Puget Sound, WA and central New Jersey. Controls were sampled from the same areas by random-digit dialing, and were frequency matched to the expected case age distribution. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using polytomous logistic regression. Among the 100 lobular cancers, 1,164 ductal cancers, and 1,501 controls, the odds ratios for oral contraceptive ever use were 1.10 (95% CI = 0.68-1.78) for lobular cancers and 1.21 (95% CI = 1.01-1.45) for ductal cancers, adjusted for study site, age at diagnosis, and pap screening history. Our results suggest that the magnitude of the association between ever use of oral contraceptives and breast cancer in young women does not vary strongly by histologic subtype. These results are similar to previous studies that report little difference in the effect of oral contraceptive use on breast cancer by histology.     

Postmenopausal estrogen and progestin use in relation to breast cancer risk.

Epidemiological evidence now consistently supports a modest increase in breast cancer risk among women using postmenopausal hormones, usually estrogens.Less is known regarding how the addition of progestin affects breast cancer risk. The objective of this study was to investigate the type and duration of postmenopausal therapy and breast cancer risk. We performed a multicenter population-based case-control study set in Massachusetts, New Hampshire, and Wisconsin. The subjects were 5298 postmenopausal women (age range, 50-79 years) with a new diagnosis of invasive breast cancer from statewide tumor registries. For comparison, 5571 controls were randomly selected from population lists. Participants completed a structured telephone interview covering hormone use and breast cancer risk factors. Multivariable regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). The RR for breast cancer increased with longer durations of hormone use, about 2%/year for estrogen alone (RR, 1.02; 95% CI, 1.01-1.03) and 4%/year for estrogen-progestin use (RR, 1.04; 95% CI, 1.01-1.08). Estrogen-progestin use that was both recent and long term (>5 years in duration) was more strongly associated with breast cancer risk (RR, 1.57; 95% CI, 1.15-2.14) than similar use of estrogen alone (RR, 1.39; 95% CI, 1.17-1.65). In estrogen-progestin users, risks were similar for sequential and continuous use regimens but perhaps stronger for lobular than ductal breast cancer. Use of progestin alone was associated with a doubling of risk (RR, 2.09; 95% CI, 1.07-4.07 for ever use versus nonuse). Estrogen-progestin use, both sequential and continuous, appears to be more strongly associated with risk of breast cancer than use of estrogen alone.     

Extra-tumoral breast tissue in breast cancer patients: variations with steroid contraceptive use

The association between oral contraceptive (OC) use and benign breast changes in extra-tumoral breast tissue was studied histologically in 1,503 breast cancer patients from The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. The occurrence of ductal hyperplasia, ductal atypia, sclerosing adenosis, cysts, apocrine metaplasia, apocrine hyperplasia, apocrine atypia, adenosis, lobular atypia, duct ectasia, calcifications, inflammatory reaction, lactational metaplasia and a high epithelial-stromal ratio was graded semi-quantitatively. Prevalence odds ratio (POR) for each histologic variable was calculated by logistic regression analyses. Patients who had ever used OC had lower occurrence of ductal hyperplasia than never users (POR 0.72 (95% CI 0.52-0.99)). Current use and more than 8 years of use was also associated with a lower prevalence of ductal hyperplasia (POR 0.40 (0.20-0.81) and POR 0.33 (0.17-0.64), respectively). Age > 35 years at first use was associated with increased prevalence of ductal carcinoma in situ (POR 2.15 (1.05-4.40)), but not of atypical ductal hyperplasia. Our results show that the effects of OC use on ductal hyperplasia in non-neoplastic breast tissue of breast cancer patients are similar to what others have found in patients with benign breast disease only. The increased prevalence of extra-tumoral ductal carcinoma in situ in breast cancer patients who started OC use at high age may possibly be explained by a longer preinvasive phase in these patients.     

Relation of regimens of combined hormone replacement therapy to lobular,ductal, and other histologic types of breast carcinoma

BACKGROUND: The incidence of invasive lobular carcinoma has been increasing among postmenopausal women in some parts of the United States. Part of this may be due to changes in classification over time. However, the use of combined (estrogen and progestin) hormone replacement therapy (CHRT) also has increased during the last decade and may account in part for the increase in invasive lobular breast carcinoma. METHODS: A large, multicenter case-control study of Caucasian and African-American women who were diagnosed at age < 65 years with their first invasive breast tumor from July 1, 1994 through April 30, 1998 was conducted. In-person interviews were conducted with 1749 postmenopausal patients, and their responses were compared with the responses of 1953 postmenopausal control women identified through random-digit dialing who met the study criteria of being postmenopausal at the time of diagnosis. Polytomous logistic regression was used to calculate the odds ratio (OR) as an estimate of the relative risk and to compute the 95% confidence interval (95%CI) associated with the use of various regimens of hormone replacement therapy (HRT) among women diagnosed with ductal breast carcinoma, lobular (or mixed lobular and ductal) breast carcinoma, and a grouping of other histologic types of breast carcinoma. RESULTS: Ever use of unopposed estrogen therapy (ERT) was not associated with an increase in the risk of any histologic type of breast carcinoma. The risk of invasive lobular breast carcinoma and the risk of breast carcinoma of the grouping of other histologies increased among women currently using CHRT (OR, 2.2; 95%CI, 1.4-3.3; and OR, 1.9; 95%CI, 1.0-3.4, respectively). The risk increase was greater for the mixed lobular-ductal type than for the pure lobular type of breast carcinoma, although the difference was not statistically significant. There was some indication that >or= 5 years of continuous CHRT (>or= 25 days per month of progestin) was associated with a higher risk of lobular breast carcinoma (OR, 2.5; 95%CI, 1.4-4.3) compared with sequential CHRT (< 25 days per month of progestin; OR, 1.5; 95%CI, 0.8-2.6). Current use of continuous CHRT was only moderately associated with risk of ductal breast carcinoma. CONCLUSIONS: Postmenopausal women who take CHRT appear to be at an increased risk of lobular breast carcinoma. Data from this study suggest that neither ERT use nor CHRT substantially increase the risk of ductal breast carcinoma among women age < 65 years.     

Increased incidence of small and well-differentiated breast tumours in post-menopausal women following hormone-replacement therapy

Exposure to hormone-replacement therapy (HRT) has consistently been associated with an increased incidence of breast cancer, particularly of small tumours. Other tumour characteristics in relation to HRT have received less scientific attention. Our aim in this population-based prospective cohort study was to assess whether HRT is associated with an increased incidence of breast-cancer subgroups defined in terms of stage, type (according to the WHO system), Nottingham grade and the Nottingham Prognostic Index (NPI). Evaluation was based on a cohort of 5,865 post-menopausal women followed for an average of 9.8 years. Twenty percent of women reported current use of HRT at the time of the baseline interview. Record linkage with the Swedish Cancer Registry and local clinical registries identified 141 incident invasive breast-cancer cases. All tumours were reclassified by 1 pathologist. The incidence of breast cancer in HRT users was 377/10(5) and in non-users 221/10(5) person-years [relative risk (RR) = 1.72, 95% confidence interval (CI) 1.17-2.52]. This risk remained statistically significant after adjustment for established risk factors in a Cox proportional hazards analysis (RR = 1.66, 95% CI 1.12-2.45). Among HRT users, there was over-representation of cases with stage I tumours (adjusted RR = 2.33, 95% CI 1.44-3.76), of lobular carcinomas (RR = 4.38, 95% CI 1.60-12.0) and of tubular tumours (RR = 4.81, 95% CI 1.37-16.8). Nottingham grade I/II carcinomas (RR = 2.02, 95% CI 1.29-3.16) and cases with NPI < or = 3.4 (RR = 2.29, 95% CI 1.41-3.72) were similarly over-represented among HRT users. Incidence of breast cancer was increased in post-menopausal women who used HRT at baseline. Among HRT users, there was over-representation of tumours that, with regard to stage, type and grade, are associated with a favourable prognosis.     

Regional variations in breast cancer incidence among California women, 1988–1997

Background: Internationally, California has some of the highest breast cancer rates; these rates also show substantial regional variations within the state. This study describes geographic breast cancer incidence patterns within California and evaluates the degree to which socioeconomic status (SES) and urbanization explain the regional variability.Methods: Invasive breast cancer cases in women 20 year of age were identified from the California Cancer Registry, for 1988–1997, then assigned to one of three regions (San Francisco Bay Area, Southern Coastal Area and the rest of California), based on residence at diagnosis. Neighborhood SES and urbanization were derived from U.S. Census data. Rate ratios (RR) and 95% confidence intervals (CI) were computed using Poisson regression. Analyses were conducted for all invasive breast cancer cases (n=176,302) and by selected histologic subtypes: ductal (n=121,619); lobular (n=13,410); mixed ductal and lobular (n=9744).Results: Compared to block groups with the lowest quartile of SES, rates were highest in block groups with high SES. Rates also were higher in suburban and city areas than in small town/rural areas. Compared to the rest of California, age- and race-adjusted rates for all breast cancer were approximately 20% higher in the San Francisco Bay Area and 10% higher in the Southern Coastal Area. After adjusting for SES and urbanization the rate ratios were reduced to near unity (RR=1.06, 95% CI: 1.03–1.09 for San Francisco Bay Area; RR=1.02, 95% CI: 0.99–1.04 for Southern Coastal Area). Rates ratios for ductal carcinomas mirrored those for all cases. For lobular cases, rate ratios remained elevated after adjustment for age, race/ethnicity, neighborhood SES and urbanization (RR=1.18, 95% CI: 1.11–1.27 for San Francisco Bay Area; RR=1.10, 95% CI: 1.04–1.17 for Southern Coastal Area). For the subset of cases with mixed ductal and lobular histologies, the rate ratio for the San Francisco Bay Area was no longer elevated after adjusting for age, race/ethnicity, SES and urbanization (RR=0.92, 95% CI: 0.84–1.01); the adjusted rate ratio for the Southern Coastal Area, however, remained elevated (RR=1.22, 95% CI: 1.12–1.32).Conclusions: Regional differences in neighborhood SES and urbanization appear to largely explain regional rate differences in California for all breast cancers and ductal carcinomas but do not fully explain geographic patterns of breast cancer with a lobular component.