Postoophorectomy Estrogen Use and Breast Cancer Risk

OBJECTIVE:: To estimate whether the protective effect of premenopausal bilateral oophorectomy on breast cancer risk is mitigated by estrogen therapy use after surgery. METHODS:: In pooled data from four population-based case-control studies spanning 1992-2007, we examined estrogen use after total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) and subsequent breast cancer risk. We identified cases of postmenopausal invasive breast cancer in women (n=10,449) aged 50-79 years from three state tumor registries and age-matched control group participants without breast cancer (n=11,787) from driver's license and Medicare lists. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and estrogen use were queried during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with multivariable logistic regression. RESULTS:: Breast cancer risk comparisons were made relative to women who experienced natural menopause and never used hormones. Overall, breast cancer risk increased 14% among women currently using estrogens after TAHBSO (OR 1.14, 95% CI 1.03-1.28), 32% for estrogen durations less than 10 years (OR 1.32, 95% CI 1.11-1.57), and 22% for estrogen initiation within 5 years of TAHBSO (OR 1.22, 95% CI 1.09-1.37). Among women who underwent early TAHBSO (younger than 40 years), 24-30% decreases in breast cancer risk were observed among both never (OR 0.70, 95% CI 0.55-0.88) and current (OR 0.76, 95% CI 0.61-0.96) estrogen users. CONCLUSION:: Unopposed estrogen use does not negate the reduction in breast cancer risk associated with early (younger than 40 years) bilateral oophorectomy. However, initiating estrogen therapy after TAHBSO at ages 45 and older can increase breast cancer risk and should be considered carefully. LEVEL OF EVIDENCE:: II.     

Breast cancer diagnosed during hormone replacement therapy

OBJECTIVE: Hormone replacement therapy (HRT) is associated with decreased breast cancer mortality despite increased incidence. We studied postmenopausal breast cancer patients to determine whether this paradox results from earlier diagnosis, biologically less aggressive tumors, or cessation of hormonal stimulation. METHODS: Demographic, clinical, pathologic, treatment, and outcome information for 455 postmenopausal breast cancer patients who had not used postmenopausal hormones was compared with that of 47 breast cancer patients who used postmenopausal hormones prior to diagnosis. RESULTS: Hormone users were significantly younger, more often white, and of lower body mass index than nonusers. Hormone users presented significantly more often with nonpalpable mammographic findings, resulting in significantly smaller tumors with less nodal involvement than nonusers. Cancers of hormone users were more commonly invasive lobular or in situ ductal and were more likely to be steroid receptor positive. Hormone users were treated with breast conservation significantly more frequently than nonusers. These differences persisted after matching for age and year of surgery and after controlling for race. At 5 years, none of the hormone users with invasive cancers had local recurrence compared with 8% of nonusers, and 7% of users had distant disease compared with 10% of nonusers. CONCLUSION: These results indicate that favorable breast cancer survival after postmenopausal hormone use might result from earlier detection through mammography. Possible hormonal influence on tumor biology and prognosis was not supported by our data.     

Breast cancer in premenopausal women: recurrence and survival rates and relationship to hormone replacement therapy.

OBJECTIVES: To determine any association between hormonal replacement therapy (HRT) usage and breast cancer recurrence and survival rates in women who were premenopausal at the time of diagnosis of breast cancer. METHODS: The study group comprised 524 women who were diagnosed with breast cancer when they were premenopausal. Of these, 277 women reached menopause before recurrence of the disease, being lost to follow-up, or reaching the end of the study. In this group, 119 women took HRT to control menopausal symptoms. The majority took combined continuous estrogen-progestin treatment. Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes, and to death from primary tumor were compared between HRT users and non-users. RESULTS: Women who used HRT after their menopause had an adjusted relative risk of recurrence or new breast cancer of 0.75 (95% confidence interval (CI), 0.29-1.95) compared to that of non-users. The relative risk of death from all causes was 0.36 (95% CI, 0.11-1.16) and that of death from primary tumor was 0.24 (95% CI, 0.05-1.14). CONCLUSION: HRT use in women who were premenopausal at the diagnosis of primary invasive breast cancer is not associated with worse outcomes in terms of breast cancer recurrence or mortality.     

Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

OBJECTIVE: Hormone replacement therapy (HRT) is commonly prescribed to alleviate the climacteric symptoms of menopause. Recent findings from the Women's Health Initiative has raised questions about the routine use of HRT due to the increased observed incidence of cardiovascular disease and of breast and ovarian cancers in the treatment arm of the trial. In the general population, the association between HRT use and risk of ovarian cancer has not yet been resolved. This association has not been evaluated in BRCA1 or BRCA2 mutation carriers who face very high lifetime risks of both breast and ovarian cancers. METHODS: We conducted a matched case-control study on 162 matched sets of women who carry a deleterious mutation in either the BRCA1 or BRCA2 gene. Women who had been diagnosed with ovarian cancer were matched to control subjects by mutation, year of birth, and age at menopause. Information on HRT use was derived from a questionnaire routinely administered to women who were found to be carriers of a mutation in either gene. Conditional logistic regression was used to estimate the association between HRT use and the risk of ovarian cancer, stratified by mutation status and type of HRT. RESULTS: Compared with those who had never used HRT, the odds ratio associated with ever use of HRT was 0.93 (95% CI = 0.56-1.56). There was no significant relationship with increasing duration of HRT use. There was a suggestion that progestin-based HRT regimens might protect against ovarian cancer (odds ratio = 0.57) but this association was not statistically significant (P = 0.20). CONCLUSION: HRT use does not appear to adversely influence the risk of ovarian cancer in BRCA mutation carriers.     

Quimioterapia neoadyuvante como tratamiento del carcinoma lobulillar mamario. ¿Ha llegado el momento del cambio?

Benefits of primary chemotherapy in cases of breast invasive ductal carcinoma are widely accepted. However, the use of this therapy is controversial in cases of lobular invasive carcinoma: response rates are very poor–but not prognosis– and cases in which the breast can be conserved are very few. We present a rare case of bilateral synchronous breast cancer, a ductal carcinoma in the right breast and a lobular carcinoma in the left breast. It illustrates very clearly the controversy in which we currently are.     

Risk-reducing strategies for breast cancer--a review of recent literature

The incidence of newly diagnosed breast cancer cases world-wide is expected to double by 2020. Risk-reducing strategies for breast cancer include lifestyle modifications, chemoprevention and surgery (bilateral mastectomy and/or oophorectomy). Lifestyle modifications include avoidance of postmenopausal obesity and hormone replacement therapy (HRT), regular physical activity, and restriction of alcohol and animal fat intake. Tamoxifen is a selective estrogen receptor modulator (SERM) shown in randomized controlled trials to reduce the incidence of estrogen receptor (ER)-positive breast cancer in high-risk healthy women. However, its routine use cannot be recommended for breast cancer prevention in healthy women due to its significant adverse effects, specifically in terms of endometrial carcinoma and thromboembolism. On the other hand, tamoxifen may be used for chemoprevention in women at high risk of developing ER-positive breast cancer and at low risk of developing complications. Raloxifene, another SERM, also appears to be effective in reducing breast cancer risk, and lacks the unwanted stimulatory effect on the uterus. Other promising chemopreventive agents currently under investigation include cyclo-oxygenase 2 (COX-2) inhibitors, fenretinide, aromatase inhibitors, and goserelin. Prophylactic mastectomy can reduce breast cancer risk by 90% in high-risk women. Bilateral oophorectomy has the potential of reducing the risk of both breast and gynecologic cancer in women carrying BRCA-1 or BRCA-2 mutations. Further research is required to identify novel strategies to prevent ER-negative breast cancer, minimize the adverse effects of tamoxifen and other SERMs, and evaluate the role of mammary ductal lavage and ductoscopy in guiding risk-reducing strategies.     

A contribution to the natural history of breast cancer. V. Bilateral primary breast cancer: incidence, risks and diagnosis of simultaneous primary cancer in the opposite breast

Tissue from contralateral breast was taken from 505 patients with invasive breast cancer. Every 5th patient had simultaneous carcinoma in the opposite breast, 7.7% (39/505) had invasive cancer, and 13.1% (66/505) had carcinoma in situ. Invasive cancers in the opposite breast were diagnosed at an earlier stage as compared with the neoplasm of the primary breast. However, 26% of the patients already had positive axillary nodes. The following risk indicators of the bilateral disease were found: age at time of diagnosis, histologic type of tumours, familial breast cancer, suspicious mammography, P2/DY-breast parenchymal pattern (Wolfe) and multicentric cancer of primary breast. Our findings support the proposal to consider bilaterality of breast cancer as a sign of systemic disease of the breasts, involving the ductal and lobular system within eight quadrants of a paired organ (Ober).     

Breast cancer risk in postmenopausal women using estrogen-only therapy

OBJECTIVE: To evaluate whether the risk of estrogen-only therapy on breast cancer varies by dose, constituent, and route of administration. METHODS: All Finnish women older than age 50 years using oral or transdermal estradiol (n=84,729), oral estriol (n=7,941), or vaginal estrogens (n=18,314) for at least 6 months during 1994-2001 were identified from the national medical reimbursement register. They were followed for breast cancer with the aid of the Finnish Cancer Registry to the end of 2002. RESULTS: Altogether, 2,171 women with breast cancer were identified. The standardized incidence ratio of breast cancer with systemic estradiol for less than 5 years was 0.93 (95% confidence interval 0.80-1.04), and for estradiol use for 5 years or more, 1.44 (1.29-1.59). Oral and transdermal estradiol was accompanied by a similar risk of breast cancer. The risk was most prominent with the dose greater than 1.9 mg/d orally; whereas the risk associated with transdermal route was not dose-dependent. The standardized incidence ratio for the lobular type of breast cancer (1.58) was slightly higher than that for the ductal type (1.36). The use of estradiol was associated with both localized breast cancer (1.45; 1.26-1.66) and cancer spread to regional nodes (1.35; 1.09-1.65). The incidence of carcinoma in situ (n=32) was increased (2.43; 1.66-3.42) among estradiol users. CONCLUSION: Estradiol for 5 years or more, either orally or transdermally, means 2-3 extra cases of breast cancer per 1,000 women who are followed for 10 years. Oral estradiol use for less than 5 years, oral estriol, or vaginal estrogens were not associated with a risk of breast cancer. LEVEL OF EVIDENCE: II-2.     

Risk factors for ovarian cancer in central Italy

OBJECTIVE: We conducted a case-control study to analyze risk factors for ovarian cancer. METHODS: Cases included 440 women (age range 13-80 years, median 54) with a histologically confirmed diagnosis of epithelial ovarian cancer who were admitted to the Gynecological Oncological Department of Gynecologic Oncology at the Catholic University Hospital in Rome, Italy. Controls were women admitted to the same hospital where cases were identified for acute nongynecological, nonhormonal, and nonneoplastic conditions. A total of 868 control women (age range 19-80 years, median 55) were interviewed. RESULTS: In comparison with ever married women, the multivariate odds ratios (OR) of ovarian cancers was 2.0 (95% confidence interval, CI 1.3-3.2) for never married women. Cases and controls were similar as regards educational status and body mass index. No clear relation emerged between ovarian cancer and age at menarche, menopausal status, and age at menopause. In comparison with nulliparae, the estimated ORs were 0.8, 0.9, and 0.7, respectively, in women reporting one, two, or three births. Women reporting two or more induced abortions were at decreased risk of ovarian cancer (OR 0.5, 95% CI 0.3-1.0). In comparison with women reporting their first birth before 20 years of age, the multivariate ORs were 1.8, 2.0, and 2.8, respectively, for women reporting their first birth at age 20-24, 25-30, and >/=31 (chi(2) trend = 10.1). Breast-feeding for more than 1 year was associated with an OR of 0.5 (95% CI, 0.4-0.8). Forty-two (9.5%) cases and 164 (18.9%) controls reported ever oral contraceptive use: in comparison with never users, the multivariate OR was 0.4 (95% CI 0.3-0.6) for ever users, and the risk decreased with duration of use. The OR for ovarian cancer was 2.9 (95% CI, 1.5-5.8) for women with a family history of the disease. CONCLUSION: This study, conducted on a relatively low-risk population, confirms the role of oral contraceptive on ovarian cancer risk and the direct association with family history of ovarian cancer. It also indicates that a later age at first birth is directly, and induced abortion and breast-feeding are inversely, related to the risk of the disease.     

Life prevalence of hormone replacement therapy and profile of users have not changed among women with self-reported menopause in the last two decades in Porto, Portugal.

OBJECTIVES: To describe the prevalence of hormone replacement therapy (HRT) in a Portuguese population by menopause date, from 1985 to 2005. METHODS: Participants were 382 postmenopausal women assessed as part of the ongoing follow-up evaluation of a cohort of Portuguese adults. Data were collected on education, lifetime use of oral contraceptives, menopause status, spontaneous or surgical menopause, and lifetime use of HRT. HRT use was analysed yearly and across 5-year menopause intervals, from 1985 to 2005. RESULTS: Overall, 40.1% of women who entered menopause between 1985 and 2005 reported having ever used HRT. No significant trend was observed throughout the 20-year period or across the 5-year intervals. Additionally, no trend was observed in HRT prevalence among women who either reported surgical or spontaneous menopause. Median education increased significantly among both HRT users and non-users; however, from 1990 onwards, HRT users were significantly more educated than non-users. CONCLUSIONS: The prevalence of use of HRT and characteristics of users among Portuguese women living in Porto and entering menopause in the last 20 years have not changed substantially.     

Compliance with hormone replacement therapy at Songklanagarind Hospital

AIM: To determine compliance with hormone replacement therapy (HRT) over a 2-year period, reasons for discontinuing HRT and the factors associated with non-compliance. METHODS: A total of 202 women attending the menopause clinic at Songklanagarind Hospital and taking HRT were included in this retrospective study. Compliance was assessed for each 6-month interval within the first 2 years. Reasons for discontinuation were requested from women who had stopped using HRT. RESULTS: Compliance rates with HRT for the study group were 57.9% at 6 months, 42.6% at 12 months, 35.1% at 18 months and 32.7% at 24 months. The main reasons for discontinuing HRT were improvement of climacteric symptoms (20.9%), fear of cancer (16.4%) and irregular bleeding (11.9%). Logistic regression analysis revealed a significant increase in the risk of non-compliance of HRT among agriculturists or untrained workers (OR 4.7, 95% CI 1.2-18.8; reference, government employees), those with delayed onset of treatment (>1 years; OR 3.0, 95% CI 1.1-8.0; reference, 0-3 months) and those prescribed HRT for climacteric symptoms or reasons other than oophorectomy or ovarian failure (OR 18.2-41.6 depending on reasons). Agriculturists or untrained workers who delayed onset of treatment for climacteric symptoms had the highest expected non-compliance rate of 0.95%. CONCLUSION: Long-term compliance of HRT was not good at Songklanagarind menopause clinic. More attention has to be paid to the counseling of patients about HRT. Agricultural or untrained workers, late starting HRT, and presence of climacteric complaints were the significant factors for poor HRT compliance.     

Patterns of use of hormone replacement therapy in one million women in Britain, 1996-2000

Objective To describe national patterns of use of hormone replacement therapy (HRT) in 1996–2000.
Design Population-based study of women aged 50–64.
Setting England and Scotland.
Population A total of 1,091,250 women were recruited between May 1996 and December 2000.
Methods Women invited for screening at 66 NHS breast screening units were sent a questionnaire to complete before they were screened; 71% of women screened participated.
Main outcome measures Prevalence of use of HRT.
Results Overall, 33% of women reported that they were currently using HRT, the average duration of use being 5.8 years; 50% were ever-users. Current use of HRT was about twice as common at age 50–54 than 60–64, but varied little by time or region, the prevalences being 33%–34% in each year from 1996 to 2000; 30% in Scotland and 35% in southeast England. The prevalence of current use of HRT varied substantially depending on the woman's history of gynaecological surgery and past health, and was as follows in women with a history of: bilateral oophorectomy (66%); hysterectomy without bilateral oophorectomy (48%); neither hysterectomy nor bilateral oophorectomy (27%); breast cancer (6%); other cancer (25%); stroke (24%); venous thromboembolism (24%); diabetes (25%); heart disease (31%); or hypertension (31%). There was considerably less variation in the prevalence of use of HRT according to deprivation index, education, parity, body mass index, exercise, smoking or alcohol consumption.
Conclusions HRT is currently used by around one-third of women aged 50–64 in Britain and appears to be influenced considerably more strongly by a woman's medical and surgical history than by socio-economic or lifestyle factors.     

Effects of hormone replacement therapy for menopause on prognostic factors of breast cancer

AIM: Hormone replacement therapy (HRT) is widely used by post-menopausal women. Although this treatment may slightly increase the incidence of breast cancer, more and more cases are diagnosed while women are taking HRT. The purpose of this study was to ascertain the influence of HRT on prognostic factors and outcome of breast cancer. Data on all breast cancer patients, including precise information on HRT, was prospectively and systematically recorded in a data base. PATIENTS AND METHODS: From 1990 to 1998, 1223 post-menopausal women fulfilled the eligibility criteria for this study. The clinical features, laboratory findings and survival rates in 245 HRT users who developed breast cancer while being treated were compared with those of 245 matched breast cancer patients who had never received HRT. RESULTS: Patients who developed breast cancer during HRT had fewer locally advanced cancers and smaller and better-differentiated cancers. Estradiol receptivity was quantitatively lower in users. Metastasis-free survival were better for the users. CONCLUSION: We conclude that HRT does not affect the prognosis of breast cancer. Regular surveillance during HRT allows early detection of smaller lesions. The higher number of well-differentiated cancers and the distribution of hormone receptivity may reflect interaction between neoplastic tissue and exogenous hormones.     

Lobular carcinoma in situ and invasive lobular cancer of the breast

PURPOSE OF REVIEW: The incidence of lobular carcinoma in situ and invasive lobular carcinoma of the breast is increasing. Recent data suggest that lobular carcinoma in situ is an indolent precursor for breast cancer, rather than a pure risk factor. This could imply free surgical margins become important. The risk of contralateral carcinoma and of multifocality of invasive lobular carcinoma is higher than for invasive ductal carcinoma. Therefore, the need for mastectomy, or even for preventative contralateral mastectomy is questioned. Conventional mammography or ultrasonography cannot always give useful preoperative information about the extent of lobular cancers. The value of dynamic contrast-enhanced magnetic resonance imaging needs to be established for these patients. RECENT FINDINGS: The risk of invasive carcinoma after lobular carcinoma in situ is increased. Invasive carcinoma is usually located at the index point of lobular carcinoma in situ and is of lobular histology. Dynamic contrast-enhanced magnetic resonance imaging can be useful in the detection and preoperative staging of invasive lobular carcinoma. The risk of local recurrence is high in patients with invasive lobular carcinoma. Mastectomy and breast reconstruction could be an option in selected patients. The response to preoperative chemotherapy is worse for invasive lobular carcinoma compared with invasive ductal carcinoma, with a greater need for rescue mastectomy. SUMMARY: Lobular carcinoma in situ and invasive lobular carcinoma are different entities from ductal carcinoma in situ and invasive lobular carcinoma. Their biological profile should be studied further in order to make the fine tuning of treatment possible.     

Attitudes toward prophylactic oophorectomy and screening utilization in women at increased risk of developing hereditary breast/ovarian cancer.

OBJECTIVES: The aim of this study was to evaluate ovarian cancer screening uptake and attitudes toward prophylactic oophorectomy in women at risk of developing hereditary breast/ovarian cancer. STUDY METHODS: Ninety-five unaffected women, who approached 1 of 14 familial cancer clinics for advice about their breast/ovarian cancer risk and surveillance and prophylactic options, were assessed in a cross-sectional design when they attended the clinic. RESULTS: Among high-risk women ages 30 and over who had not had a prophylactic oophorectomy, 48% reported ever having had an ovarian ultrasound, and among women ages 50 and over 23% had had a serum CA 125 test. Twenty-three percent of women would consider, and 27% would not consider, a prophylactic oophorectomy should the genetic test indicate a germline mutation associated with hereditary breast/ovarian cancer, while 38% were unsure. Twelve percent had already undergone a prophylactic oophorectomy. Interest in prophylactic oophorectomy was associated with increased breast/ovarian cancer anxiety (chi(2) = 5.14, P = 0.023), but not objective cancer risk (chi(2) = 0.40, P = 0.53). CONCLUSION: Findings demonstrate that breast/ovarian cancer anxiety, rather than objective risk, is the major factor which determines women's attitude to prophylactic oophorectomy. Women are likely to benefit from interventions aimed at reducing breast/ovarian cancer anxiety. Research on the impact of prophylactic oophorectomy would be helpful in the development of educational strategies and decision aids to assist women who are trying to make a decision under conditions of uncertainty.     

A population-based study of squamous cell vaginal cancer: HPV and cofactors.

BACKGROUND: Little is known about the etiology of in situ or invasive squamous cell cancer of the vagina. It is thought that some vaginal cancers may have the same etiology as cervical cancer. It is also not known whether in situ and invasive vaginal cancer share the same etiologic factors. We conducted a study to evaluate risk factors for in situ and invasive vaginal cancer and their potential relationship to prior exposure to human papillomaviruses (HPV). METHODS: A population-based case-control study included 156 women with squamous cell in situ or invasive vaginal cancer diagnosed between January 1981 and June 1998 and 2041 control women identified through random-digit dialing in western Washington state. Cases and controls were interviewed in person and provided blood samples; archival tumor tissue was retrieved for cases. Blood samples were tested for antibodies to HPV, and tumor tissue was tested for HPV DNA. RESULTS: Women with vaginal cancer were more likely to have five or more lifetime sexual partners (OR = 3.1, 95% CI 1.9 to 4.9), to have an early age at first intercourse (<17 years OR = 2.0, 95% CI 1.2 to 3.5), and to be current smokers at diagnosis (OR = 2.1, 95% CI 1.4 to 3.1) than control women. Approximately 30% of all cases had been treated for a prior anogenital tumor, most often of the cervix. Prior hysterectomy was a risk factor only among women who had no history of prior anogenital cancer (OR = 3.9 95% CI 2.5 to 6.1). Antibodies to HPV16 L1 were strongly related to risk of vaginal cancer (OR = 4.3, 95% CI 3.0 to 6.2). We detected HPV DNA in tumor blocks from over 80% of the patients with in situ and 60% of the patients with invasive cancers. CONCLUSIONS: In situ and invasive vaginal neoplasia have many of the same risk factors as cervical cancer, including a strong relationship to HPV infection. Women who have been treated for a prior anogenital cancer, particularly of the cervix, have a high relative risk, although low absolute risk, of being diagnosed with vaginal cancer.     

Hormonal replacement therapy after gynaecological cancer

Thousands of women are treated each year for gynaecological cancers; many of these are already in menopause, while other younger patients will go into early menopause due to surgery, chemotherapy and/or radiotherapy to the pelvic region. The aim of this paper is to review the biological and clinical evidence in favour and against hormone replacement therapy (HRT) use after gynaecological cancers. With the exception of breast and endometrial cancer, there is no biological evidence that HRT may increase the recurrence risk. In women with previous endometrial cancer, HRT use is not supported by univocal and conclusive data to formulate specific recommendations, whereas most authors suggest that oestrogens may be used after adequate information about risks and benefits. The use of HRT in breast cancer patients is, at present, considered contra-indicated, even if results of clinical trials are not concordant. Therapeutic non-hormonal alternatives may be proposed to these patients.     

Hormone replacement therapy: a 2008 perspective

New clinical data and recent re-analyses of data from the Women’s Health Initiative (WHI) have greatly changed the perception of hormone replacement therapies (HRTs) since the media excitedly reported the first findings of the combined HRT arm of WHI in 2002. The initial adverse finding of an overall early increase in cardiovascular risk in both WHI and the Women’s International Study of long Duration Oestrogen after Menopause in women who start or recommence HRT on average 13–14 years after menopause has been overshadowed by recent evidence supporting a cardioprotective effect of HRT when it is commenced near menopause. Most HRT is commenced in this early ‘therapeutic window’ when coronary calcification and atherosclerosis appear to be inhibited by oestrogen. Some neuroprotective effects are also hypothesised when HRT is commenced at this time. The effect of HRT on stroke when prescribed near menopause is not clear as it is uncommon at this age.A doubling in the risk of thromboembolism is still the main risk of HRT. The absolute risk is small near menopause when thromboembolic risk factors are not present and may be much less with non-oral routes. Breast cancer is a fear for many users but WHI showed a reduction of eight breast cancers per annum per 10,000 women years in oestrogen-only users at 7 years and no significant increase in first-time users of combined HRT until after 7 years when it was 8/10,000 per annum or less than 0.1%.Weight gain in users of HRT and placebo is similar around menopause.The main indications for HRT remain the control of menopausal symptoms where quality of life is gained and for the prevention of osteoporotic fractures, particularly in younger menopausal women where the risks are low. Other benefits include a reduction in diabetes and death.HRT must be individualised and tailored to minimise the start-up symptoms of bleeding on combined continuous regimens and breast tenderness when oestrogen levels are too high. Menopausal therapies are moving towards safer regimens, which minimise or eliminate systemic progestogen, safer routes (non-oral), safer lower doses and safer women.     

Bilateral breast cancer. Incidence and risk factors

OBJECTIVE: To clarify, thanks to a retrospective study of 24 bilateral breast cancer cases, the frequency, the risk factors and the prognosis of bilateral breast cancers. PATIENTS AND METHOD: Between 1984 and 1999, out of 506 patients treated for unilateral non-metastatic breast cancer at Gynecologic and Obstetric ward, at Maternity Souissi of Rabat, 24 cases of bilateral breast cancers were diagnosed. Our results were compared to those of the literature. RESULTS: The frequency of bilateral breast cancers was 4.7% (24/506). In 87.5% of cases, these were metachronous cancers with a mean interval of 45 months (12-144 months). Patients under 40 at first cancer ran a fivefold superior risk than women more than 40 (P < 0.05). In cases of T3 or T4 tumors, the risk was 10-fold superior to that in smaller ones (P < 0.05). DISCUSSION AND CONCLUSION: Significantly more first metachronous tumors were invasive adenocarcinoma cancers. Histologic type of first and second tumor was the same in all cases. The prognosis depends at once on the first and second cancer staging and the treatment must be done according to the same rules as in the first cancer.