Critically Appraised Topic:
Does Hormone Replacement Therapy increase the risk of breast cancer or total mortality in women with a family history of breast cancer?
Appraised by: Deb Bynum, MD
Date: December 16, 1997
Clinical Bottom Lines:
1. In the prospective cohort study, 12.2 % of the women sampled reported a family history of breast cancer (mother or sister). HRT use in women with a family history was not associated with an increased risk of breast cancer and was associated with a significantly reduced total mortality rate.
2. Early age at menarche, late age at first birth, high waist-to-hip ratio, high BMI, college education, and alcohol intake were associated with increased risk for breast cancer.
3. Among women with a family history of breast cancer, those who currently used HRT (and had for at least 5 years) developed breast cancer at an age-adjusted annual rate of 61 cases per 10,000 person-years compared to a 46 per 10,000 person-years rate in women who had never used HRT; these rates were not statistically different.
4. Women with a family history and on HRT had a significantly lower total mortality than did women who had never used HRT (RR .67, CI .51-.89). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10,000 person-years compared to a rate of 80 deaths per 10,000 person-years.
5. Women with no family history of breast cancer who received HRT also had a reduced mortality rate (51 per 10,000 person-years vs 70 per 10,000 person-years).
6. Suggestion that women with a family history of breast cancer who had used HRT had an increased risk of death from breast cancer in evaluation of cause-specific mortality (this was based on only 84 deaths and not statistically significant).
The Evidence: Observational study based upon a cohort of patients selected from a random sample of all women between ages 55 and 69 with a valid driver’s license; information was based upon questionnaires returned by 41837 women (42.7% response). Women who were premenopausal, had had a mastectomy or any history of cancer other than skin cancer, or had an unkown family history were excluded leaving 35919 women in the at-risk cohort for analysis.
| Use of HRT | No Family History of Breast Cancer | Family History of Breast Cancer | ||
| Cases | multivariate-adjusted RR (CI) | Cases | multivariate adjusted RR | |
| Post-menopausal breast cancer cases and RR | ||||
| never | 528 | 1.00 | 97 | 1.00 |
| former (<5 yrs) | 202 | 1.01 (.85-1.2) | 45 | 1.19 (.81-1.73) |
| former (>5 yrs) | 27 | .80 (.53-1.19) | 8 | 1.17 (.55-2.47) |
| current(<5 yrs) | 41 | 1.31 (.94-1.83) | 7 | 1.37 (.59-3.18) |
| current(>5 yrs) | 67 | 1.13 (.86-1.5) | 13 | 1.35 (.72-2.53) |
| Total mortality, cases and RR | ||||
| never | 1140 | 1.00 | 194 | 1.00 |
| former (<=5 yrs) | 408 | .86 (.76-.97) | 56 | .71 (.51-.98) |
| former (>5 yrs) | 62 | .76 (.57-1.00) | 6 | .59 (.30-1.16) |
| former (<=5 yrs) | 51 | 1.00 (.75-1.35) | 2 | .24 (.06-.97) |
| current(>5 yrs) | 91 | .84 (.67-1.06) | 11 | .55 (.28-1.07) |
Comments:
1. Bottom line, little if any risk with increase in breast cancer with HRT seen in postmenopausal women who had no prior history of cancer, regardless of family history. Observation that women on HRT have a lower overall mortality holds true.
2. Difficult to assess risk factors given overall low number of cases in the population.
3. Early -onset breast cancer is more strongly associated with family history than is late-onset breast cancer-- this study excluded women under the age of 55 (this study does not address the risk in younger women in whom family history is more of a factor)
4. Issues of detection /surveillance bias exist -- there was an increased use of mammography in women with a family history of breast cancer and on HRT; the study reports no difference in extent of disease at diagnosis which raises new set of questions related to screening.
Sellars, TA, Mink PJ, Cerhan JR, Zheng W, Anderson KE, Kushi LH, Folsom AR. The Role of Hormone Replacement Therapy in the Risk for Breast Cancer and Total Mortality in Women with a Family History of Breast Cancer. Ann Int Med 1997; 127: 973-980.