Abstract P1-09-05: The RAZOR trial: a phase II prevention trial of screening plus goserilin and raloxifene versus screening alone in pre-menopausal women at increased risk of breast cancer.

Abstract Background: Observational studies indicate that oophorectomy at about age 40 reduces breast cancer risk by approximately a half in high risk women. Widespread use of risk reducing oophorectomy is unlikely to be acceptable to these women. We explored the feasibility of giving goserelin to produce reversible ovarian suppression together with raloxifene to maintain bone mineral density (BMD). Objectives: The primary study objective was adherence to treatment. Secondary objectives were uptake of randomisation, side effects/quality of life and measures of effect on bone and in serum. Methods: Recruitment was from 3 UK Family History Clinics. Consenting women at ≥ 1 in 3 lifetime risk of breast cancer were randomised to control or monthly subcutaneous goserelin 3.6 mg and raloxifene 60 mg/d orally for two years. Questionnaires (Endocrine Symptom Checklist, Trait &amp; State Anxiety, Sexual Activity &amp; Cancer Worry) measuring toxicity/quality of life were administered by nurses. Dual energy X-ray absorptiometry (DXA) BMD measurements were performed in the treatment arm annually. Lipids and collagen breakdown products were measured by standard methods. Results: 75 of 511 (14.7%) women approached agreed to randomisation (38 to treatment and 37 to control). The major reason for non-entry was fear of side effects (85%). Median age was 37 and 35 years, for the experimental (A) and control arm (B), respectively. Median follow up is 8.8 years. 20/38 in arm A and 27/37 of controls completed the 24 m study. 18/38 women in arm A withdrew (13 [34%] because of side effects) and 10/37 in arm B for various reasons including the desire for risk reducing surgery (n = 4). No significant differences were seen in the Endocrine Symptom Sub-scale, State or Trait anxiety or Cancer Worry. However, Hot flushes, night and cold sweats (together p &amp;lt;0.005), vaginal dryness (p = 0.006); loss of interest in sex, dyspareunia and reduced sexual pleasure (together p &amp;lt; 0.005) were significantly more in arm A. Despite this, 11 of 23 women in arm A when asked would have been happy to complete a potential five years of treatment. BMD declined by 3–7% and Ctx significantly increased (p &amp;lt; 0.005 each) but both returned to baseline by year 3. Lipids were unchanged. 4 women later developed breast cancer in arm B and 2 in arm A. Conclusions: Uptake and adherence to treatment was relatively low in this group of women at high risk. The major reason for low uptake was fear of side effects and these were the major reason for drop out from treatment. Raloxifene did not maintain BMD. This approach to breast cancer prevention induced significant symptoms and bone loss, thus methods to ameliorate these need to be developed if ovarian suppression is to play a role in breast cancer prevention. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-09-05.</jats:p

Long-Term Evaluation of Women Referred to a Breast Cancer Family History Clinic (Manchester UK 1987–2020)

Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million. In this review, we report the outcome of risk assessment, screening and prevention strategies in the clinic and propose future approaches. Between 1987–2020, 14,311 women were referred, of whom 6.4% were from known gene families, 38.2% were at high risk (≥30% lifetime risk), 37.7% at moderate risk (17–29%), and 17.7% at an average/population risk who were discharged. A total of 4168 (29.1%) women were eligible for genetic testing and 736 carried pathogenic variants, predominantly in BRCA1 and BRCA2 but also other genes (5.1% of direct referrals). All women at high or moderate risk were offered annual mammographic screening between ages 30 and 40 years old: 646 cancers were detected in women at high and moderate risk (5.5%) with a detection rate of 5 per 1000 screens. Incident breast cancers were largely of good prognosis and resulted in a predicted survival advantage. All high/moderate-risk women were offered lifestyle prevention advice and 14–27% entered various lifestyle studies. From 1992–2003, women were offered entry into IBIS-I (tamoxifen) and IBIS-II (anastrozole) trials (12.5% of invitees joined). The NICE guidelines ratified the use of tamoxifen and raloxifene (2013) and subsequently anastrozole (2017) for prevention; 10.8% women took up the offer of such treatment between 2013–2020. Since 1994, 7164 eligible women at ≥25% lifetime risk of breast cancer were offered a discussion of risk-reducing breast surgery and 451 (6.2%) had surgery. New approaches in all aspects of the service are needed to build on these results.</jats:p

Long-term evaluation of women referred to a breast cancer family history clinic (Manchester UK 1987–2020)

Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million. In this review, we report the outcome of risk assessment, screening and prevention strategies in the clinic and propose future approaches. Between 1987–2020, 14,311 women were referred, of whom 6.4% were from known gene families, 38.2% were at high risk (≥30% lifetime risk), 37.7% at moderate risk (17–29%), and 17.7% at an average/population risk who were discharged. A total of 4168 (29.1%) women were eligible for genetic testing and 736 carried pathogenic variants, predominantly in BRCA1 and BRCA2 but also other genes (5.1% of direct referrals). All women at high or moderate risk were offered annual mammographic screening between ages 30 and 40 years old: 646 cancers were detected in women at high and moderate risk (5.5%) with a detection rate of 5 per 1000 screens. Incident breast cancers were largely of good prognosis and resulted in a predicted survival advantage. All high/moderate-risk women were offered lifestyle prevention advice and 14–27% entered various lifestyle studies. From 1992–2003, women were offered entry into IBIS-I (tamoxifen) and IBIS-II (anastrozole) trials (12.5% of invitees joined). The NICE guidelines ratified the use of tamoxifen and raloxifene (2013) and subsequently anastrozole (2017) for prevention; 10.8% women took up the offer of such treatment between 2013–2020. Since 1994, 7164 eligible women at ≥25% lifetime risk of breast cancer were offered a discussion of risk-reducing breast surgery and 451 (6.2%) had surgery. New approaches in all aspects of the service are needed to build on these results

Mammographic surveillance in women aged 35-39 at enhanced familial risk of breast cancer (FH02)

Although there have been encouraging recent studies showing a potential benefit from annual mammography in women aged 40-49 years of age with an elevated breast cancer risk due to family history there is little evidence of efficacy in women age

Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic

BACKGROUND: Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. METHODS: All eligible women between 33 and 46 years at ⩾17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. RESULTS: Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a ‘cancer drug', and daily reminder of cancer risk. CONCLUSIONS: Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others