Progestins and breast cancer

Title: Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk
Author: C. Schairer, et al
Address: Rockville, MD 
Source: JAMA 283: 485-491 (January) 2000

Summary:A total of 46,355 postmenopausal women were studied to determine if the increased risk of breast cancer associated with the estrogen-progestin regimen is greater than those associated with estrogen alone. The average age of participants was 58 years and the average length of follow-up was 10.2 years. During the time period studied, 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 with relative risk (RR) 1.2 for estrogen only and 1.4 for estrogen-progestin only. The RR increased by 0.01 with each year of estrogen only use and by 0.08 with each year of estrogen-progestin. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only. Researchers concluded that their data indicated that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.
Comment: A relative risk of 1 suggests that there is neither an increase nor decrease in an event happening. A RR of 1.2 indicates a 20% increase, or in this study, from about 4% to about a 5% chance of developing breast cancer. Most studies thus far have hovered around RR of 1, most very slightly above 1. In evaluating the value of estrogen replacement, a useful comparison is that there are 4 times as many women who die as a result of a hip fracture than breast cancer. The above adds data, still total benefit versus total risk should be considered.

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Plant estrogens and breast cancer

Title: Phytoestrogens and breast cancer in postmenopausal women: A case control study 
Author: A. Murkies, et al.
Address: Victoria, Australia 
Source: Menopause: The Journal of the North American Manopause Society 7:289-296 (Sept./Oct.) 2000

Summary: Eighteen women with recently diagnosed breast cancer before surgery and 20 controls were used to help researchers examine the relationship between isoflavones, androgens, and dietary composition and the risk of breast cancer in Australian postmenopausal women. Both groups of women were evaluated for urinary isoflavones, serum and urinary sex steroids, and dietary intake. Researchers found that the women with breast cancer had lower 24-hour urinary daidzein when compared with the controls, and there was a tendency to lower urinary genistein excretion. Women with breast cancer also had a higher total testosterone level. However, no significant differences were found for serum sex hormone binding globulin, free androgen index, dehydroepiandrosterone sulfate, estradiol and progesterone, or in urinary androgen metabolites, or in dietary intake with regard to fat, carbohydrate, protein, or fiber consumption. It was concluded that these findings agree with the increasing observational data demonstrating a protective effect from phytoestrogens on breast cancer risk. The ASRM believes that “many individuals might benefit from including more legumes and whole grains in their diets and eating fewer refined foodstuffs.”

Comment: Whether there is a protective effect of plant estrogens on breast cancer is very much undecided. Commercial concerns are spending millions trying to convince us that there is. The question surely cannot be decided by the above study of 20 patients. Despite an attempt to control for various confounding variables, there still remains considerable bias in patient selection. It is interesting that diets were not different in cancer patients. From where did the isoflavones come?

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Worrisome ovarian cysts

Title: Worrisome ovarian cysts 
Author: W. Gotlieb, et al.
Address: Tel Hashomer, Israel 
Source: American Journal of Obstetrics and Gynecology 183:541-546 (September) 2000

Summary: Researchers performed a retrospective analysis of ultrasonographic characteristics and CA 125 levels in 91 patients with ovarian tumors of borderline malignancy. In 75% of the patients, serous tumors of borderline malignancy were associated with elevated CA 125 levels, compared with 30% of mucinous tumors. In stage IA serous tumors, CA 125 was elevated in 35% of patients, compared with 89% of tumors that had spread beyond the ovary. Mucinous tumors were larger on ultrasonography than serous tumors. Mucinous tumors were also multilocular in half the patients and contained papillations in 40%. Serous tumors were multilocular in 30%, but presented with solid or papillary patterns in 78%. A resistance index of less than 0.4 was found in 36% of mucinous tumors and half the cases of serous tumors. In 13%, ultrasonographic traits were compatible with a simple cyst, including 1 patient with microinvasion and 1 patient with stage IIIB disease. Sensitivity of gray-scale ultrasonography was 87% that of CA 125 measurement was 62%, and that of flow was 55%. At least 1 diagnostic test result was abnormal in 93%, 2 were abnormal in 69%, and all 3 were abnormal in 21%. A high proportion of borderline tumors of the ovary, particularly of the serous type, were associated with elevated CA 125 levels and abnormal ultrasonographic characteristics, although some tumors presented as simple cysts.

Comment: The great fear is that a cyst found on ultrasound is cancerous. While this is rare in the woman of reproductive age, it does occur. This study was particularly distressing because some of the borderline tumors and 2 cancers were associated with “simple cysts,” i.e. those with a thin wall and none of the usual signs that raise suspicion. Persistent cysts should not be dismissed and a CA 125 seems to be a relatively good 2nd step.