MEDLINE Abstracts: Hormone Replacement Therapy and Breast Cancer
MEDLINE Abstracts: Hormone Replacement Therapy and Breast Cancer
What's the latest in hormone replacement therapy and breast cancer? Find out in this easy-to-navigate collection of recent MEDLINE Abstracts compiled by the editors at Medscape Pharmacotherapy.
Ross RK, Paganini-Hill A, Wan PC, Pike MC
J Natl Cancer Inst. 2000;16;92(4):328-32
Background: Hormone replacement therapy (HRT) given as unopposed estrogen replacement therapy (ERT) gained widespread popularity in the United States in the 1960s and 1970s. Recent prescribing practices have favored combination HRT (CHRT), i.e., adding a progestin to estrogen for the entire monthly cycle (continuous combined replacement therapy [CCRT]) or a part of the cycle (sequential estrogen plus progestin therapy [SEPRT]). Few data exist on the association between CHRT and breast cancer risk. We determined the effects of CHRT on a woman's risk of developing breast cancer in a population-based, case-control study.
Methods: Case subjects included those with incident breast cancers diagnosed over 4(1/2) years in Los Angeles County, CA, in the late 1980s and 1990s. Control subjects were neighborhood residents who were individually matched to case subjects on age and race. Case subjects and control subjects were interviewed in person to collect information on known breast cancer risk factors as well as on HRT use. Information on 1897 postmenopausal case subjects and on 1637 postmenopausal control subjects aged 55-72 years who had not undergone a simple hysterectomy was analyzed. Breast cancer risks associated with the various types of HRT were estimated as odds ratios (ORs) after adjusting simultaneously for the different forms of HRT and for known risk factors of breast cancer. All P values are two-sided.
Results: HRT was associated with a 10% higher breast cancer risk for each 5 years of use (OR(5) = 1.10; 95% confidence interval [CI] = 1.02-1.18). Risk was substantially higher for CHRT use (OR(5) = 1.24; 95% CI = 1.07-1.45) than for ERT use (OR(5) = 1. 06; 95% CI = 0.97-1.15). Risk estimates were higher for SEPRT (OR(5) = 1.38; 95% CI = 1.13-1.68) than for CCRT (OR(5) = 1.09; 95% CI = 0. 88-1.35), but this difference was not statistically significant.
Conclusions: This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have important implications for the risk-benefit equation for HRT in women using CHRT.
Panico S, Galasso R, Celentano E, et al
Am J Public Health. 2000; Sep;90(9):1397-402
Objectives: An analysis was performed to determine the risks and benefits of a 10-year hormone replacement therapy regimen that had been applied to all women at 50 years of age in 8 countries.
Methods: Cumulative mortality with and without hormone replacement therapy over 20 years was estimated, with both current and predicted total and disease-specific secular mortality trends and the influence of a generational cohort effect taken into account.
Results: In countries with high ischemic heart disease frequency and predictable relative predominance of ischemic heart disease rates over breast cancer rates for the next 20 years, hormone replacement therapy could result in benefits with regard to overall mortality; this advantage decreases in younger-generation cohorts. In countries in which breast cancer mortality predominates over ischemic heart disease in early postmenopause and in which the predictable trends for both diseases reinforce this condition, a negative effect on overall mortality would be observed. In the United States, the effect of large-scale hormone replacement therapy would change over time.
Conclusions: The long-term effect of hormone replacement therapy on life expectancy of postmenopausal women may vary among countries.
Li CI, Weiss NS, Stanford JL, Daling JR
Cancer. 2000; Jun 1;88(11):2570-7
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.
Schairer C, Lubin J, Troisi R, et al
JAMA. 2000;283(4):485-91
Context: Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown.
Objective: To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone.
Design: Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program.
Setting: Twenty-nine screening centers throughout the United States.
Participants: A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years).
Main Outcome Measure: Incident breast cancers by recency, duration, and type of hormone use.
Results: During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only.
Conclusion: Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.
Natrajan PK, Soumakis K, Gambrell RD Jr
Am J Obstet Gynecol. 1999;181(2):288-95
Objective: We sought to review the status of patients with breast cancer who were treated with estrogen replacement therapy and compare the results with those of nonestrogenic hormone users and women not treated with hormone replacement.
Study Design: The study group consisted of 76 patients with breast cancer, including 50 using estrogen replacement for up to 32 years, 8 using nonestrogenic hormone replacement for up to 6 years and followed for up to 11 years, and 18 using no hormones for up to 10 years. In addition to estrogen use, 40 of the 50 hormone users were treated with androgens, usually in the form of implantation of testosterone pellets. Forty-five subjects were also given progestogens, usually megestrol acetate 20 to 40 mg for 10 to 25 days each month. The 8 nonestrogen hormone users were treated with various combinations of testosterone pellets, tamoxifen, and progestogens. Forty-two of the 50 estrogen users are still being treated in our clinic, as are 2 of the 8 subjects using nonestrogen hormone. Follow-up was done through the tumor registry at University Hospital, and those whose tumor records were not current were telephoned.
Results: Of the 50 estrogen users, 3 have died (a mortality rate of 6%), and the rest have been followed for 6 months to 32 years, with a mean duration of follow-up of 83.3 +/- 8.81 months. One of the 8 nonestrogen hormone users has died (a mortality rate of 12.5%), and the rest have been followed for 2 to 11 years, with a mean duration of follow-up of 72.0 +/- 5. 93 months. Six of the 18 women not using hormone replacement have died (a mortality rate of 33.3%), and the rest have been followed for 6 months to 10 years, with a mean duration of follow-up of 50.5 +/- 6.01 months.
Conclusion: Estrogen replacement therapy apparently does not increase either recurrences or mortality rates. Adding progestogens may even decrease recurrences. Women with early breast cancer should be offered hormone replacement therapy after a full explanation of the benefits, risks, and controversies.
[No authors listed.]
Oncology. 1999;13(2):245-8, 251-4, 257
There are several million breast cancer survivors worldwide. In the United States, 180,000 women were diagnosed with breast cancer in 1997, and approximately 97,000 of these women have an extremely low chance of suffering a recurrence of their cancer. With an average age at diagnosis of 60 years and a 25-year expected duration of survival, the current number of breast cancer survivors in the United States may approach 2.5 million women. Since breast cancer is now being detected at an earlier stage than previously and since adjuvant chemotherapy may cause ovarian failure, an increasing number of women are becoming postmenopausal at a younger age after breast cancer treatment. This conference was convened in September 1997 to consider how menopausal breast cancer survivors should be treated at the present time and what future studies are needed to develop improved therapeutic strategies. A total of 59 breast cancer experts and patient advocates participated. The proceedings of the conference will be published in six installments in successive issues of ONCOLOGY. The first part, published last month, defined the problem and explored its magnitude and ramifications for patient management. This second part focuses on the benefits and risks of hormone replacement therapy (HRT) in patients with breast cancer.
Colditz GA
J Natl Cancer Inst. 1998;90(11):814-23
We sought to determine the strength of the evidence suggesting that estrogen and postmenopausal replacement hormones play a role in the development of breast cancer. We reviewed the existing English language literature in MEDLINE on hormones and breast cancer, including reports on cell proliferation and endogenous hormone levels, as well as epidemiologic studies of the relationship between the use of postmenopausal hormones and the risk of breast cancer in women. A factor that increases the probability that cancer will develop in an individual has been defined as a cancer cause. The Hill criteria for demonstrating a link between environmental factors and disease were used to review the evidence for a causal relationship between female hormones and breast cancer. We found evidence of a causal relationship between these hormones and breast cancer, based on the following criteria: consistency, dose-response pattern, biologic plausibility, temporality, strength of association, and coherence. The magnitude of the increase in breast cancer risk per year of hormone use is comparable to that associated with delaying menopause by a year. The positive relationship between endogenous hormone levels in postmenopausal women and risk of breast cancer supports a biologic mechanism for the relationship between use of hormones and increased risk of this disease. The finding that the increase in risk of breast cancer associated with increasing duration of hormone use does not vary substantially across studies offers further evidence for a causal relationship. We conclude that existing evidence supports a causal relationship between use of estrogens and progestins, levels of endogenous estrogens, and breast cancer incidence in postmenopausal women. Hormones may act to promote the late stages of carcinogenesis among postmenopausal women and to facilitate the proliferation of malignant cells. Strategies that do not cause breast cancer are urgently needed for the relief of menopausal symptoms and the long-term prevention of osteoporosis and heart disease.
What's the latest in hormone replacement therapy and breast cancer? Find out in this easy-to-navigate collection of recent MEDLINE Abstracts compiled by the editors at Medscape Pharmacotherapy.
Ross RK, Paganini-Hill A, Wan PC, Pike MC
J Natl Cancer Inst. 2000;16;92(4):328-32
Background: Hormone replacement therapy (HRT) given as unopposed estrogen replacement therapy (ERT) gained widespread popularity in the United States in the 1960s and 1970s. Recent prescribing practices have favored combination HRT (CHRT), i.e., adding a progestin to estrogen for the entire monthly cycle (continuous combined replacement therapy [CCRT]) or a part of the cycle (sequential estrogen plus progestin therapy [SEPRT]). Few data exist on the association between CHRT and breast cancer risk. We determined the effects of CHRT on a woman's risk of developing breast cancer in a population-based, case-control study.
Methods: Case subjects included those with incident breast cancers diagnosed over 4(1/2) years in Los Angeles County, CA, in the late 1980s and 1990s. Control subjects were neighborhood residents who were individually matched to case subjects on age and race. Case subjects and control subjects were interviewed in person to collect information on known breast cancer risk factors as well as on HRT use. Information on 1897 postmenopausal case subjects and on 1637 postmenopausal control subjects aged 55-72 years who had not undergone a simple hysterectomy was analyzed. Breast cancer risks associated with the various types of HRT were estimated as odds ratios (ORs) after adjusting simultaneously for the different forms of HRT and for known risk factors of breast cancer. All P values are two-sided.
Results: HRT was associated with a 10% higher breast cancer risk for each 5 years of use (OR(5) = 1.10; 95% confidence interval [CI] = 1.02-1.18). Risk was substantially higher for CHRT use (OR(5) = 1.24; 95% CI = 1.07-1.45) than for ERT use (OR(5) = 1. 06; 95% CI = 0.97-1.15). Risk estimates were higher for SEPRT (OR(5) = 1.38; 95% CI = 1.13-1.68) than for CCRT (OR(5) = 1.09; 95% CI = 0. 88-1.35), but this difference was not statistically significant.
Conclusions: This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have important implications for the risk-benefit equation for HRT in women using CHRT.
Panico S, Galasso R, Celentano E, et al
Am J Public Health. 2000; Sep;90(9):1397-402
Objectives: An analysis was performed to determine the risks and benefits of a 10-year hormone replacement therapy regimen that had been applied to all women at 50 years of age in 8 countries.
Methods: Cumulative mortality with and without hormone replacement therapy over 20 years was estimated, with both current and predicted total and disease-specific secular mortality trends and the influence of a generational cohort effect taken into account.
Results: In countries with high ischemic heart disease frequency and predictable relative predominance of ischemic heart disease rates over breast cancer rates for the next 20 years, hormone replacement therapy could result in benefits with regard to overall mortality; this advantage decreases in younger-generation cohorts. In countries in which breast cancer mortality predominates over ischemic heart disease in early postmenopause and in which the predictable trends for both diseases reinforce this condition, a negative effect on overall mortality would be observed. In the United States, the effect of large-scale hormone replacement therapy would change over time.
Conclusions: The long-term effect of hormone replacement therapy on life expectancy of postmenopausal women may vary among countries.
Li CI, Weiss NS, Stanford JL, Daling JR
Cancer. 2000; Jun 1;88(11):2570-7
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.
Schairer C, Lubin J, Troisi R, et al
JAMA. 2000;283(4):485-91
Context: Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown.
Objective: To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone.
Design: Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program.
Setting: Twenty-nine screening centers throughout the United States.
Participants: A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years).
Main Outcome Measure: Incident breast cancers by recency, duration, and type of hormone use.
Results: During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only.
Conclusion: Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.
Natrajan PK, Soumakis K, Gambrell RD Jr
Am J Obstet Gynecol. 1999;181(2):288-95
Objective: We sought to review the status of patients with breast cancer who were treated with estrogen replacement therapy and compare the results with those of nonestrogenic hormone users and women not treated with hormone replacement.
Study Design: The study group consisted of 76 patients with breast cancer, including 50 using estrogen replacement for up to 32 years, 8 using nonestrogenic hormone replacement for up to 6 years and followed for up to 11 years, and 18 using no hormones for up to 10 years. In addition to estrogen use, 40 of the 50 hormone users were treated with androgens, usually in the form of implantation of testosterone pellets. Forty-five subjects were also given progestogens, usually megestrol acetate 20 to 40 mg for 10 to 25 days each month. The 8 nonestrogen hormone users were treated with various combinations of testosterone pellets, tamoxifen, and progestogens. Forty-two of the 50 estrogen users are still being treated in our clinic, as are 2 of the 8 subjects using nonestrogen hormone. Follow-up was done through the tumor registry at University Hospital, and those whose tumor records were not current were telephoned.
Results: Of the 50 estrogen users, 3 have died (a mortality rate of 6%), and the rest have been followed for 6 months to 32 years, with a mean duration of follow-up of 83.3 +/- 8.81 months. One of the 8 nonestrogen hormone users has died (a mortality rate of 12.5%), and the rest have been followed for 2 to 11 years, with a mean duration of follow-up of 72.0 +/- 5. 93 months. Six of the 18 women not using hormone replacement have died (a mortality rate of 33.3%), and the rest have been followed for 6 months to 10 years, with a mean duration of follow-up of 50.5 +/- 6.01 months.
Conclusion: Estrogen replacement therapy apparently does not increase either recurrences or mortality rates. Adding progestogens may even decrease recurrences. Women with early breast cancer should be offered hormone replacement therapy after a full explanation of the benefits, risks, and controversies.
[No authors listed.]
Oncology. 1999;13(2):245-8, 251-4, 257
There are several million breast cancer survivors worldwide. In the United States, 180,000 women were diagnosed with breast cancer in 1997, and approximately 97,000 of these women have an extremely low chance of suffering a recurrence of their cancer. With an average age at diagnosis of 60 years and a 25-year expected duration of survival, the current number of breast cancer survivors in the United States may approach 2.5 million women. Since breast cancer is now being detected at an earlier stage than previously and since adjuvant chemotherapy may cause ovarian failure, an increasing number of women are becoming postmenopausal at a younger age after breast cancer treatment. This conference was convened in September 1997 to consider how menopausal breast cancer survivors should be treated at the present time and what future studies are needed to develop improved therapeutic strategies. A total of 59 breast cancer experts and patient advocates participated. The proceedings of the conference will be published in six installments in successive issues of ONCOLOGY. The first part, published last month, defined the problem and explored its magnitude and ramifications for patient management. This second part focuses on the benefits and risks of hormone replacement therapy (HRT) in patients with breast cancer.
Colditz GA
J Natl Cancer Inst. 1998;90(11):814-23
We sought to determine the strength of the evidence suggesting that estrogen and postmenopausal replacement hormones play a role in the development of breast cancer. We reviewed the existing English language literature in MEDLINE on hormones and breast cancer, including reports on cell proliferation and endogenous hormone levels, as well as epidemiologic studies of the relationship between the use of postmenopausal hormones and the risk of breast cancer in women. A factor that increases the probability that cancer will develop in an individual has been defined as a cancer cause. The Hill criteria for demonstrating a link between environmental factors and disease were used to review the evidence for a causal relationship between female hormones and breast cancer. We found evidence of a causal relationship between these hormones and breast cancer, based on the following criteria: consistency, dose-response pattern, biologic plausibility, temporality, strength of association, and coherence. The magnitude of the increase in breast cancer risk per year of hormone use is comparable to that associated with delaying menopause by a year. The positive relationship between endogenous hormone levels in postmenopausal women and risk of breast cancer supports a biologic mechanism for the relationship between use of hormones and increased risk of this disease. The finding that the increase in risk of breast cancer associated with increasing duration of hormone use does not vary substantially across studies offers further evidence for a causal relationship. We conclude that existing evidence supports a causal relationship between use of estrogens and progestins, levels of endogenous estrogens, and breast cancer incidence in postmenopausal women. Hormones may act to promote the late stages of carcinogenesis among postmenopausal women and to facilitate the proliferation of malignant cells. Strategies that do not cause breast cancer are urgently needed for the relief of menopausal symptoms and the long-term prevention of osteoporosis and heart disease.
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