Ovarian cancer risk in premenopausal and perimenopausal women treated with Tamoxifen: a case-control study

As tamoxifen stimulates ovarian steroidogenesis in premenopausal women, induces ovulation and increases the incidence of benign ovarian cysts, there has been concern that it might also increase ovarian cancer risk in women treated premenopausally. In a national case-control study in Britain, treatment histories were collected for 158 cases of ovarian cancer after breast cancer diagnosed at ages under 55 years and 464 controls who had breast cancer at these ages without subsequent ovarian cancer. Risk of ovarian cancer was not raised for women overall who had taken tamoxifen (odds ratio (OR)=0.9, 95% confidence interval (CI) 0.6-1.3) or for those treated when premenopausal (OR=1.0, 95% CI 0.6-1.6) or perimenopausal (OR=0.7, 95% CI 0.2-2.4). There was also no relation of risk to daily dose, duration or cumulative dose of tamoxifen, or time since last use. There was, however, a significantly raised risk in relation to non-hormonal chemotherapy. The results suggest that tamoxifen treatment of premenopausal or perimenopausal women does not materially affect ovarian cancer risk, but that non-hormonal chemotherapy might increase risk.     

The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands

BACKGROUND: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. PATIENTS AND METHODS: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using standardised incidence ratios (SIRs), cumulative incidence and Cox regression analysis, adjusted for competing risks. RESULTS: Median follow-up was 5.8 years, in which 624 CBC occurred <6 months after the index cancer (synchronous) and 1,477 thereafter (metachronous). Older age and lobular histology were associated with increased synchronous CBC risk. Standardised incidence ratio (SIR) of CBC was 2.5 (95% confidence interval (95% CI) 2.4-2.7). The SIR of metachronous CBC decreased with index cancer age, from 11.4 (95% CI 8.6-14.8) when <35 to 1.5 (95% CI 1.4-1.7) for > or =60 years. The absolute excess risk of metachronous CBC was 26.8/10,000 person-years. The cumulative incidence increased with 0.4% per year, reaching 5.9% after 15 years. Adjuvant hormonal (Hazard rate ratio (HR) 0.58; 95% CI 0.48-0.69) and chemotherapy (HR 0.73; 95% CI 0.60-0.90) were associated with a markedly decreased CBC risk. A metachronous CBC worsened survival (HR 1.44; 95% CI 1.33-1.56). CONCLUSION: Young breast cancer patients experience high synchronous and metachronous CBC risk. Adjuvant hormonal or chemotherapy considerably reduced the risk of CBC. CBC occurrence adversely affects prognosis, emphasizing the necessity of long-term surveillance directed at early CBC-detection.     

No breast cancer subgroup can be spared postoperative radiotherapy after breast-conserving surgery. Fifteen-year results from the Swedish Breast Cancer Group randomised trial,SweBCG 91 RT

BackgroundBreast-conserving surgery (BCS) followed by radiotherapy (RT) is an established treatment for women with T1-2N0 breast cancers. Since subgroups of patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is important to study whether RT is necessary for all patients.Patients and methodsA total of 1187 women with primary T1-2N0M0 breast cancer were randomised, after standardised sector resection, to postoperative whole breast RT or no local treatment. Adjuvant systemic therapy was offered to patients with stage II cancers. Patients were followed with clinical examinations and annual mammography for 10 years and thereafter referred to the Swedish mammography screening program.ResultsAfter 15 years of follow-up, a higher cumulative incidence of IBTR was observed in control patients, 23.9%, versus irradiated patients, 11.5%, P < 0.001. Recurrence-free survival was inferior, 51.7% versus 60.4%, P = 0.0013. The main effect of RT was seen during the first 5 years. However, overall survival was not significantly lower 68.4% versus 71.1%, P = 0.68, nor was breast cancer–specific mortality significantly higher.ConclusionsRT after BCS significantly reduced the incidence of IBTR at 15 years of follow-up. We were unable to identify subgroups which could be spared RT. Breast cancer mortality was not significantly reduced after RT. Good predictive markers for radiation sensitivity and improved adjuvant systemic therapy are needed to omit RT after BCS.     

Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Combined effects of goserelin and tamoxifen on estradiol level,breast density,and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial

Background:

This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer.

Methods:

This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and randomly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months. Contralateral BD was also measured at 0, 12, and 18 months.

Results:

Five participants dropped out of the goserelin plus TAM group, and two participants dropped out of the TAM-alone group before initiation of endocrine therapy. The rest of patients received scheduled treatment and 3 years of median follow-up. No serious adverse effects were observed, and only two local recurrences have been observed in these patients. Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group (P<0.05). The endometrium in the goserelin plus TAM group was significantly thinner than that in the TAM-alone group (P<0.05), and women in the TAM-alone group exhibited endometrial thickening over the course of the study. Furthermore, no significant differences in blood lipid levels were reported between the two groups.

Conclusion:

The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level, followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer, which may eventually lead to better outcome in these patients.     

Tamoxifen alters the plasma concentration of molecules associated with cardiovascular risk in women with breast cancer undergoing chemotherapy

Objectives.

The objective of this study was to evaluate the effect of tamoxifen on blood markers that are associated with cardiovascular risk, such as C-reactive protein (CRP), apolipoprotein A-1 (Apo-A), and apolipoprotein B-100 (Apo-B), in women undergoing chemotherapy for breast cancer.

Methods.

Over a period of 12 months, we followed 60 women with breast cancer. The women were divided into the following groups: a group that received only chemotherapy (n = 23), a group that received chemotherapy plus tamoxifen (n = 21), and a group that received only tamoxifen (n = 16). Plasma CRP levels were assessed at 0, 3, 6, and 12 months, and Apo-A and Apo B levels as well as the Apo-B/Apo-A ratio were assessed at 0 and 12 months.

Results.

We found increases in the plasma concentration of CRP in the chemotherapy alone and chemotherapy plus tamoxifen groups after 3 and 6 months of treatment (before the introduction of tamoxifen). However, after 12 months of treatment, women who used tamoxifen (the chemotherapy plus tamoxifen and tamoxifen alone groups) showed a significant reduction in CRP and Apo-B levels and a decrease in the Apo-B/Apo-A ratio. A significant increase in serum Apo-A levels was observed in the group receiving chemotherapy alone as a treatment for breast cancer.

Conclusion.

The use of tamoxifen after chemotherapy for the treatment of breast cancer significantly reduces the levels of cardiovascular disease risk markers (CRP, Apo-B, and the Apo-B/Apo-A ratio).     

Aromatase inhibitor plus ovarian suppression as adjuvant therapy in premenopausal women with breast cancer

The goal of adjuvant hormonal therapy for breast cancer is to prevent recurrence by eradicating micrometastatic disease. Recent studies have shown that the use of aromatase inhibitors (AIs) as adjuvant therapy improves outcomes for postmenopausal women with estrogen receptor (ER)-positive breast cancer compared to adjuvant endocrine therapy with tamoxifen alone. The research question has been raised whether AIs would have similar improvements in disease-free survival (DFS) in premenopausal women with ER-positive breast cancer. Combining 2 phase 3 clinical trials (n = 4,690), Pagani and colleagues randomized premenopausal women with ER-positive early breast cancer to exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 y. After a median follow-up of 68 months, DFS was 91.1% in the AI group and 87.3% in the tamoxifen group. In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence.     

Toremifene in the treatment of breast cancer

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier (SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase III trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events and it has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.     

Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial.

BACKGROUND: To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen. PATIENTS AND METHODS: Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease. RESULTS: Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation. CONCLUSIONS: The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients.     

Yoga for persistent fatigue in breast cancer survivors: a randomized controlled trial

BACKGROUND:

Cancer‐related fatigue afflicts up to 33% of breast cancer survivors, yet there are no empirically validated treatments for this symptom.

METHODS:

The authors conducted a 2‐group randomized controlled trial to determine the feasibility and efficacy of an Iyengar yoga intervention for breast cancer survivors with persistent post‐treatment fatigue. Participants were breast cancer survivors who had completed cancer treatments (other than endocrine therapy) at least 6 months before enrollment, reported significant cancer‐related fatigue, and had no other medical conditions that would account for fatigue symptoms or interfere with yoga practice. Block randomization was used to assign participants to a 12‐week, Iyengar‐based yoga intervention or to 12 weeks of health education (control). The primary outcome was change in fatigue measured at baseline, immediately post‐treatment, and 3 months after treatment completion. Additional outcomes included changes in vigor, depressive symptoms, sleep, perceived stress, and physical performance. Intent‐to‐treat analyses were conducted with all randomized participants using linear mixed models.

RESULTS:

Thirty‐one women were randomly assigned to yoga (n = 16) or health education (n = 15). Fatigue severity declined significantly from baseline to post‐treatment and over a 3‐month follow‐up in the yoga group relative to controls (P = .032). In addition, the yoga group had significant increases in vigor relative to controls (P = .011). Both groups had positive changes in depressive symptoms and perceived stress (P < .05). No significant changes in sleep or physical performance were observed.

CONCLUSIONS:

A targeted yoga intervention led to significant improvements in fatigue and vigor among breast cancer survivors with persistent fatigue symptoms. Cancer 2012. © 2011 American Cancer Society.     

Multiparity and the risk of premenopausal breast cancer: different effects across ethnic groups in Singapore

Background The relationship between multiparity and premenopausal breast cancer risk is different in Caucasian, African-American and Hispanic women. For Asian women, this relationship has never been well studied. Methods Within the Singapore Birth Registry, we selected all women who had a first child between 1986 and 2002 (169,936 Chinese, 40,521 Malay, 17,966 Indian). We linked them to the Singapore Cancer Registry data to identify those who developed breast cancer after childbirth (n = 527). We used multivariate Cox analysis to examine the relationship between parity, ethnicity and premenopausal breast cancer risk. Results Compared to Chinese, Malay women had increased and Indian women had decreased risks of premenopausal breast cancer (adjusted Hazard Ratios [HRadj] 1.25 [1.0–1.6] and 0.48 [0.3–0.8] respectively). Multiparity did not modify the risk of premenopausal breast cancer in Chinese and Indians. In Malays there was a significant risk reduction with increasing parity (P _trend 0.037). Malay women with one, two and ≥3 children had premenopausal breast cancer risks (HR_adj) of 1.86 (1.2–3.0), 1.52 (1.1–2.2) and 0.87 (0.6–1.3) respectively compared to their Chinese counterparts. Conclusions The impact of multiparity on premenopausal breast cancer risk differs across ethnic groups in Singapore. Increasing parity reduces the risk of premenopausal breast cancer in Malay, but not in Chinese and Indian women. Uniparous Malay women have twice the risk of premenopausal breast cancer compared to uniparous Chinese. This excess risk disappears after giving birth to ≥3 children. Indian women have lower premenopausal breast cancer risks than Chinese, regardless of their parity status. Helena M. Verkooijen and Karen P. L. Yap are joint first authors.     

Endocrine therapy in premenopausal women with breast cancer: a critical appraisal of current evidence

Nearly 60% of all breast cancer premenopausal women are diagnosed with a hormone receptor positive tumor and, therefore, are candidates for adjuvant hormonal therapy. Treatment with tamoxifen for at least 5 years has been for a long time the standard of care, as it is associated with overall positive clinical outcomes. However, in the last decade, a number of studies on adjuvant endocrine therapy in premenopausal women with hormone receptor positive breast cancer have been published, adding a bulk of evidence to existing knowledge in this field. A critical appraisal of their results appears necessary in order to put the recently collected data into the current framework of treatment, and to discuss the several issues that remain open. Here, we review the most recent evidence on the following: the optimal duration of tamoxifen treatment, results of the studies comparing tamoxifen alone to tamoxifen plus ovarian function suppression (OFS), results of the studies comparing tamoxifen plus OFS to aromatase inhibitors plus OFS.     

Genetic variation in DNA repair pathway genes and premenopausal breast cancer risk

Purpose We comprehensively evaluated genetic variants in DNA repair genes with premenopausal breast cancer risk. Methods In this nested case–control study of 239 prospectively ascertained premenopausal breast cancer cases and 477 matched controls within the Nurses’ Health Study II, we evaluated 1,463 genetic variants in 60 candidate genes across five DNA repair pathways, along with DNA polymerases, Fanconi Anemia complementation groups, and other related genes. Results Four variants were associated with breast cancer risk with a significance level of <0.01; two in the XPF gene and two in the XRCC3 gene. An increased risk was found in those harboring a greater number of missense putative risk alleles (a priori defined in an independent study) in the non-homologous end-joining (NHEJ) repair pathway of double-strand breaks (odds ratio (OR) per risk allele, 1.37 (95% confidence interval (CI), 1.03–1.82), P trend, 0.03). Conclusions This study implicates variants of genes in the double-strand break repair pathway in the etiology of premenopausal breast cancer. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update

Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80%, and following the first diagnosis the 10-year risk of contralateral breast cancer is approximately 30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30-0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65).     

A randomised controlled trial of a psychoeducational intervention for women at increased risk of breast cancer

This study aimed to compare the impact of two versions of a psychoeducational written intervention on cancer worry and objective knowledge of breast cancer risk-related topics in women who had been living with an increased risk of familial breast cancer for several years. Participants were randomised to three conditions: scientific and psychosocial information pack (Group 1), scientific information pack only (Group 2) or standard care control (Group 3). They completed postal questionnaires at baseline (n=163) and 4 weeks (n=151). As predicted, there was a significant decrease in cancer worry for Group 1, but not Group 2. Objective knowledge significantly improved for both Group 1 and Group 2 as expected, but not Group 3. However, there was an unpredicted decline in cancer worry for Group 3. This study supports the value of a scientific and psychosocial information pack in providing up-to-date information related to familial risk of breast cancer for long-term attendees of a familial breast cancer clinic. Further research is warranted to determine how the information pack could be incorporated into the existing clinical service, thus providing these women with the type of ongoing psychosocial support that many familial breast cancer clinics are currently lacking.     

Change of mammographic density predicts the risk of contralateral breast cancer - a case-control study

Introduction

Mammographic density is a strong risk factor for breast cancer, but it is unknown whether density at first breast cancer diagnosis and changes during follow-up influences risk of non-simultaneous contralateral breast cancer (CBC).

Methods

We collected mammograms for CBC-patients (cases, N = 211) and unilateral breast cancer patients (controls, N = 211), individually matched on age and calendar period of first breast cancer diagnosis, type of adjuvant therapy and length of follow-up (mean follow-up time: 8.25 years). The odds of CBC as a function of changes of density during follow-up were investigated using conditional logistic regression, adjusting for non-dense area at diagnosis.

Results

Patients who experienced ≥10% absolute decrease in percent density had a 55% decreased odds of CBC (OR = 0.45 95% CI: 0.24 to 0.84) relative to patients who had little or no change in density from baseline to first follow-up mammogram (mean = 1.6 (SD = 0.6) years after diagnosis), whereas among those who experienced an absolute increase in percent density we could not detect any effect on the odds of CBC (OR = 0.83 95% CI: 0.24 to 2.87).

Conclusion

Decrease of mammographic density within the first two years after first diagnosis is associated with a significantly reduced risk of CBC, this potential new risk predictor can thus contribute to decision-making in follow-up strategies and treatment.     

Cardiac toxicity events in the PHARE trial,an adjuvant trastuzumab randomised phase III study

BackgroundThis article reports, the cardiac toxicity according to 6- versus 12-month durations of adjuvant trastuzumab in PHARE randomised trial (NCT00381901).Patients and methodsCardiac follow-up and Left Ventricular Ejection Fraction (LVEF) assessment by echocardiography or multigated acquisition scan were performed every 3 months while patients received trastuzumab and after completion of treatment over the first 2 years and every 6 months afterwards. The primary cardiac end-point was Cardiac Heart Failure (CHF) defined as New York Heart Association (NYHA) class III or IV. The secondary cardiac end-points were: cardiac events, cardiac dysfunctions defined by NYHA class I and II; LVEF decreases, cardiac recoveries. The cardiac subcommittee reviewed cardiac events and assessed if patients had favourable outcomes or not on the basis of trends from LVEF measurements.ResultsAmong 3380 patients the cardiac dysfunction assessment included 14,055 and 13,218 LVEF measurements in the 12- and 6-month arms. The overall incidences of CHF were 0.65% (11/1690) and 0.53% (9/1690) in the 12 and 6 month arms, respectively (p > 0.05). Cardiac dysfunction occurred in 5.9% (100/1690) and 3.4% (58/1690) of patients in the 12 and 6 month arms, respectively (p = 0.001). Recoveries were observed for the majority patients and 0.79% (27/3380) of patients experienced an unfavourable cardiac outcome.ConclusionPHARE confirm that the incidence of cardiac end-points remains low and mostly reversible after trastuzumab. Identification at baseline of cardiac risk categories of patients should be of interest to provide an optimal adaptation of adjuvant modalities and a shorter duration might be an option.     

A mobile shield to reduce scatter radiation to the contralateral breast during radiotherapy for breast cancer: preclinical results

Purpose: To design a practical breast shield and to investigate its efficacy in reducing scattered radiation to the contralateral breast of patients undergoing radiation therapy for breast cancer.

Methods and Materials: We constructed a mobile shield consisting of (a) a mobile base and a counterweight; (b) a vertical column adjustable in height and a diagonal arm adjustable in angle; (c) a curved, 2.5-cm thick lead sheet with a 1-cm thick polystyrene liner for blocking scattered radiation; and (d) diode detectors to verify that the edge of the lead sheet is not in the useful beam in addition to the use of the field light. Measurements were performed with thermoluminescent dosimeters on 10 patients without the shield and on an anthropomorphic phantom with a pair of wax breasts with and without the shield. All of the patients were treated with 6-MV photons (Varian 6/100). The scattered radiation from the medial and lateral fields was measured separately.

Results: The contribution of the medial field to the total scattered dose was 70% to 75%, whether a medial wedge was used or not. However, without a medial wedge, the scattered dose was reduced by nearly 33% at 3 to 9 cm away from the medial border. In the anthropomorphic phantom study with wax breast, the mobile shield reduced the medial field contribution to the total scatter dose to less than the contribution from the lateral field without a shield. With a prescribed dose of 50 Gy and a medial wedge, the median scatter dose to the contralateral breast from 6 patients was 5.3 Gy; without a medial wedge, it was 3.8 Gy from 4 patients at 6 cm from the medial border. In the phantom study, with the shield the total dose to the contralateral breast was 1.0 Gy at 6 cm from the medial border with a same prescribed dose.

Conclusion: The mobile shield reduced the scatter dose to the contralateral breast from the linear accelerator (Varian 6/100, 6-MV photons) by a factor of 3 to 4. The shield greatly reduced the scattered dose in the wax phantom. Equivalent reductions in patients may be clinically significant by reducing the risk of radiation-induced breast cancer in the contralateral breast of woman undergoing radiation therapy for breast cancer. The shield is safe and easy to adjust to each patient.     

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.