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Background: Vasomotor symptoms (hot flushes and night sweats) are experienced by more than two-thirds of women with breast cancer taking oral adjuvant endocrine therapy. Safe and effective treatments are lacking. Q-122 is a novel, non-hormonal compound that has shown promise for reducing vasomotor symptoms by modulation of oestrogen-responsive neurons in the hypothalamus. We aimed to assess the efficacy and safety of Q-122 in women with breast cancer taking oral adjuvant endocrine therapy and experiencing vasomotor symptoms., Methods: We conducted a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial at 18 sites in Australia, New Zealand, and the USA. Eligible participants were women, aged 18-70 years, taking a stable dose of tamoxifen or an aromatase inhibitor following breast cancer and experiencing at least 50 self-reported moderate to severe vasomotor symptoms per week. Participants were randomly assigned (1:1) using an interactive web response system to oral Q-122 100 mg or identical placebo, twice daily for 28 days. Randomisation was stratified by BMI (≤30 kg/m 2 or >30 kg/m 2 ) and use of any of a selective serotonin reuptake inhibitor, selective norepinephrine reuptake inhibitor, gabapentin, or pregabalin. Q-122 and placebo capsules were identical in appearance and containers identically labelled. During the double-blind treatment and analysis phases, the participants, investigators, clinical research organisation staff, and sponsor were masked to treatment allocation. The primary outcome was the difference in the mean percentage change from baseline in the Vasomotor Symptom Severity Score of moderate and severe hot flushes and night sweats (msVMS-SS) between Q-122 and placebo after 28 days of treatment. Primary analysis was by modified intention-to-treat and safety was assessed in all participants receiving at least one dose of study drug. This study is registered at ClinicalTrials.gov, NCT03518138., Findings: Between Oct 24, 2018, and Sept 9, 2020, 243 patients were screened, 131 of whom were randomly assigned and received treatment (Q-122 n=65 and placebo n=66). Q-122 resulted in a significantly greater mean percentage change in msVMS-SS from baseline over 28 days of treatment compared with placebo (least squares mean: Q-122 -39% [95% CI -46 to -31] vs placebo -26% [-33 to -18]; p=0·018). Treatment-emergent adverse events were generally mild to moderate and similar between the two groups (treatment-related treatment-emergent adverse events in 11 [17%] of 65 patients in the Q-122 group vs nine [14%] of 66 in the placebo group); zero patients in the Q-122 group and two (3%) patients in the placebo group had serious adverse events., Interpretation: Q-122 is an effective and well tolerated non-hormonal oral treatment for vasomotor symptoms in women taking oral adjuvant endocrine therapy after breast cancer. Our results support the conduct of larger and longer studies of Q-122, with potential use extending to postmenopausal women who require an alternative to menopausal hormone therapy., Funding: QUE Oncology., Competing Interests: Declaration of interests AV is an employee of QUE Oncology. AL was an employee of QUE Oncology. RJB reports receiving honoraria for serving on medical advisory boards for Pfizer, Besins, Viatris, Theramex, and Mayne Health and for delivering lectures at educational meetings sponsored by Pfizer, Abbott, Viatris, and Besins. RJB has received institutional grant funding from Pfizer, Novogen, QUE Oncology, and Madorra. BGAS reports receiving honoraria for lectures from Besins and has received institutional grant funding from QUE Oncology. MGW is a consultant for QUE Oncology. VS reports participation on an advisory board for Novartis, is the chair of the data safety monitoring board for AstraZeneca, and has received institutional grant funding from AbbVie, Biocept, Novartis, Pfizer, Puma Biotechnology, and QUE Oncology. MH reports grants from the National Health and Medical Research Council (NHMRC) Australia and has received institutional grant funding from QUE Oncology and Madorra. SRD is an NHMRC senior principal research fellow (grant number 1135843). SRD reports grants from the NHMRC Australia; personal fees for educational activities from Besins Healthcare, Abbott Chile, BioFemme, Biosyent, and Lawley Pharmaceuticals; personal advisory board or consultancy fees from Theramex, Abbott Laboratories, Astellas, Southern Star Research, Mayne Pharma, Roche Diagnostics, Lawley Pharmaceuticals, QUE Oncology, and Gedeon Richter; and has received institutional grant funding from QUE Oncology and Ovocabio research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The recent Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) publication calculated the attributable risk of breast cancer from use of estrogen alone and estrogen plus a synthetic progestogen for less than 5 to 15 or more years of use. This CGHFB report calculated attributable risk based on their findings of relative risk from pooled data from 58 studies. Notably, neither the CGHFBC nor other previous studies have examined the effect of underlying risk of breast cancer on attributable risk. This omission prompted us to determine the magnitude of the effect of underlying risk on attributable risk in this perspective. Meaningful communication of the potential risk of menopausal hormonal therapy requires providing women with the estimated risk above their existing underlying risk (ie, attributable risk). Therefore, we have estimated attributable risks from the data published by the CGHFBC, taking into account varying degrees of underlying risk. Based on the Endocrine Society Guideline on Menopausal Hormone Therapy (MHT), we divided groups into 3 categories of risk: low (1.5%), intermediate (3.0%), and high (6.0%) underlying risk of breast cancer over 5 years. In women taking estrogen plus a synthetic progestogen for 5 to 9 years, the attributable risks of MHT increased from 12, to 42, to 85 additional women per 1000 in the low-, intermediate-, and high-risk groups, respectively. The attributable risks for estrogen alone were lower but also increased based on underlying risk. Notably, the attributable risks were amplified with duration of MHT use, which increased both relative risk and breast cancer incidence., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Little is known of the impact of aromatase inhibitor (AI) therapy on sexual and pelvic floor function., Aim: To document the prevalence of, and factors associated with, low desire, sexually related personal distress, hypoactive sexual desire dysfunction (HSDD), and pelvic floor dysfunction in women 10 years after breast cancer diagnosis., Methods: This was a prospective, observational, community-based cohort study of Australian women with invasive breast cancer recruited within 12 months of diagnosis. 1,053 of the 1,305 who completed the initial 5 years of study follow-up agreed to be re-contacted, and 992 of these women alive 10 years after diagnosis were sent the study questionnaire., Outcomes: The main outcome measure was HSDD determined by a score no higher than 5.0 on the desire domain of the Female Sexual Function Index (FSFI) plus a score of at least 11.0 on the Female Sexual Distress Scale-Revised (FSDS-R). Pelvic floor disorders, including urinary incontinence, fecal incontinence, and pelvic organ prolapse, were assessed using validated questionnaires. Multivariable logistic regression was used to assess factors associated with low desire, personal distress, and HSDD., Results: 625 completed questionnaires were returned. The respondents' median age was 65.1 years (range = 36.4-95.5). Current AI use was reported by 10% and tamoxifen use was reported by 3.4%. 521 of the 608 women (85.7%; 95% CI = 82.9-88.5) who competed the FSFI desire domain had low sexual desire, and 246 of the 563 women (43.7%; 95% CI = 39.6-47.8%) who completed the FSDS-R had sexually related personal distress. 221 of the 559 women (39.5%; 95% CI = 35.5-43.6%) who completed the 2 questionnaires had HSDD. Current AI users were more likely to have HSDD than non-users (55.2% [95% CI = 42.2-68.1] vs 37.8% [95% CI = 33.5-42.0]; P = .01). HSDD was more prevalent in sexually active, current AI users (66.7%; 95% CI = 49.4-83.9) vs current non-users (43.6%; 95% CI = 37.0-50.2; P = .02). In a logistic regression model, HSDD was significantly associated with current AI use and inversely associated with age. Fecal incontinence was more prevalent in AI users than in current non-users (29.8% [95% CI = 17.8-41.8] vs 16.4% [95% CI = 13.2-19.6], respectively; P = .01)., Clinical Implications: It is important to address women's sexual health even many years after their breast cancer diagnosis., Strengths and Limitations: Strengths include a representative sample, use of validated questionnaires, and few missing data. Limitations include sexual activity being a 4-week recall., Conclusions: AI use is associated with HSDD and fecal incontinence in women who are 10 years after breast cancer diagnosis. Robinson PJ, Bell RJ, Christakis MK, et al. Aromatase Inhibitors Are Associated With Low Sexual Desire Causing Distress and Fecal Incontinence in Women: An Observational Study. J Sex Med 2017;14:1566-1574., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Review evidence to guide management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly., Evidence: Randomized controlled clinical trials, observational studies, evidence-based guidelines, and expert opinion from professional societies., Background: Symptoms and clinical problems associated with estrogen depletion-sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia, and osteoporosis-confront the estimated 9.3 million breast cancer survivors globally., Recommendations: Following breast cancer, women should not generally be treated with menopausal hormone therapy or tibolone but should optimize lifestyle. Women with moderate to severe symptoms may benefit from mind-brain behavior or nonhormone, pharmacologic therapy. The selective serotonin/noradrenaline reuptake inhibitors and gabapentenoid agents improve VMS and quality of life. For osteoporosis, nonhormonal agents are available. Treatment of VVA remains an area of unmet need. Low-dose vaginal estrogen is absorbed in small amounts with blood levels remaining within the normal postmenopausal range but could potentially stimulate occult breast cancer cells, and although poorly studied, is not generally advised, particularly for those on aromatase inhibitors. Intravaginal dehydroepiandrosterone and oral ospemiphene have been approved to treat dyspareunia, but safety after breast cancer has not been established. Vaginal laser therapy is being used for VVA but efficacy from sham-controlled studies is lacking. Therapies undergoing development include lasofoxifene, neurokinin B inhibitors, stellate ganglion blockade, vaginal testosterone, and estetrol., Conclusions: Nonhormone options and therapies are available for treatment of estrogen depletion symptoms and clinical problems after a diagnosis of breast cancer. Individualization of treatment is essential., (Copyright © 2017 Endocrine Society)

Objectives: To investigate the awareness of breast cancer (BCa) and BCa screening amongst women at midlife in Bangladesh., Methods: A nationally representative cross-sectional survey of women aged 30-59 years was conducted in 7 districts of the 7 divisions in Bangladesh, using a multistage cluster sampling technique. The factors associated with the awareness of BCa and breast assessment of asymptomatic women were investigated separately, using multivariable logistic regression., Results: Of the 1590 participants, mean age 42.3 (±8.0) years, 81.9% had ever heard of BCa and 64.2% of any methods of BCa screening, respectively. Awareness of BCa was associated with being aged 40-49 years (adjusted OR 2.04, 95% CI 1.46-2.84), aged 49-59 years (1.96, 1.32-2.91), being overweight (1.46, 1.07-2.01) and obesity (1.62, 1.01-2.62), while inversely associated with rural dwelling (0.37, 0.22-0.61), primary education (0.44, 0.27-0.70), having no education (0.23, 0.14-0.36) and parity (0.62, 0.44-0.87). Of the 750 women who were aware of clinical breast examination (CBE) or mammography, reasons provided for not undergoing screening included that they had no symptoms (92%) and that they did not know screening was needed (40%). 8% of women reported CBE. Women with no education were less likely to have undergone CBE (0.38, 0.141.04; p=0.059)., Conclusion: Lack of understanding of the assessment of asymptomatic women is the key obstacle to BCa screening uptake in Bangladesh. Health education programs, especially BCa awareness programs, have the potential to increase BCa awareness and down-staging of the disease., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Whether moderate to severe obesity (body mass index (BMI)≥30 to <40kg/m(2)) contributes to breast cancer recurrence and mortality remains uncertain., Subjects and Methods: 1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and ≥40) were excluded from the analysis., Results: Of the 1155 included women, mean age, 58.4±11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR=1.71, 95%CI, 1.12-2.62, p=0.014), disease beyond Stage 1 (HR=2.87, 95% CI 1.73-4.75, p<0.001), OAET (HR=0.26, 95%CI 0.14-0.46, p<0.001), mastectomy (HR=3.28, 95%CI 1.98-5.44, p<0.001) and radiotherapy (HR=2.12, 95%CI 1.24-3.63, p=0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48-7.03, p=0.003) and OAET use (HR 0.41, 95%CI 0.17-0.98, p=0.046) were significantly associated with an event., Conclusion: Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: We investigated the prevalence and severity of menopausal symptoms, nearly 6 years from diagnosis, in women who had not experienced recurrent breast cancer or a new primary breast cancer (active disease) and were no longer taking oral adjuvant endocrine therapy (OAET)., Methods: A total of 1,683 women recruited within 12 months of diagnosis with invasive breast cancer completed an enrollment questionnaire and five annual follow-up questionnaires. Only women who had never reported active disease and were not taking OAET at their fifth follow-up were included in the analysis. Women previously recruited to a study of sex steroid levels provided community control data. Menopausal symptoms were assessed with the Menopause-Specific Quality of Life Questionnaire (MenQOL)., Results: Eight hundred forty-three women without active disease and not taking OAET completed the fifth follow-up questionnaire, on average, 5.8 years after diagnosis. Most had stage I (59.5%) and hormone receptor-positive disease (77.9%) at diagnosis and were postmenopausal (92.8%). Those aged 50 to 59 years were more likely to report any symptoms (P = 0.01) and more severe symptoms (P < 0.001) than older and younger women. There was no independent impact of chemotherapy on MenQOL vasomotor and sexual domain scores. Women with breast cancer had significantly higher vasomotor domain (P ≤ 0.002) and sexual domain (P ≤ 0.004) scores than community controls., Conclusions: Vasomotor and sexual symptoms are highly prevalent in breast cancer survivors and are not simply a function of OAET or chemotherapy. Given the adverse impact of these symptoms, effective interventions are needed to alleviate them in women who have completed their breast cancer treatment.

Background: Management of older women with breast cancer (BC) is challenging, as age-related comorbidities may limit treatment. We present 5-year follow-up data from women aged 70 years or older (70+), at the time of diagnosis of their BC, compared with younger women (<70 years)., Methods: Data is from an Australian cohort study of women with their first episode of invasive BC (Bupa study). Participants completed an enrollment questionnaire (EQ) within 12 months of diagnosis and annual follow-up questionnaires (FQ) for 5 years (FQ1-5). Data collected included details of the BC and its treatment. Psychological wellbeing was measured by the Psychological General Wellbeing Index (PGWB)., Results: At diagnosis, 274 (16%) women were aged 70+ and of them, 90% were aged 70-79 years. Compared with women aged <70 years, the women aged 70+ were less likely to have positive nodes, they were less likely to receive radiotherapy and chemotherapy and were more likely to have pre-existing cardiovascular morbidities. By FQ5 women aged 70+ were less likely to be taking oral adjuvant endocrine therapy (OAET) and were more likely to have died from causes other than BC. At FQ5, women 70+ reported less anxiety and better self-control., Conclusions: Women aged 70+, compared to <70 years, had less advanced disease, received radiation and chemotherapy less often, were more likely to have cardiovascular disease at the time of diagnosis, were less likely to be taking OAET at the 5-year assessment, and were more likely to die of causes other than breast cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: The aim of our study was to establish the prevalence of breast pain persisting 5 years after the initial treatment of breast cancer (BC) and the relationship between those persistent symptoms and general well-being., Methods: The study involved women from Victoria, Australia, who had survived at least 5 years from diagnosis, remained free from recurrence or new BC and completed the fifth annual follow-up questionnaire. Analysis involved both multivariable logistic and linear regression., Results: Of 1,205 women, 45 % reported breast pain which persisted for at least 3 months following initial treatment, and of these, 80 % reported pain persisting for at least 5 years. The factor contributing most to the likelihood of persistent breast pain was current lymphedema; however, a full multivariable model explained <10 % of the likelihood of breast pain persisting for 5 years. The presence of breast pain at 5 years was associated with only a modest reduction in general well-being., Conclusions: Breast pain persisting for at least 5 years after treatment for BC is common. As the pain is largely unexplained by factors associated with the characteristics of the cancer or its treatment, the contribution of patient expectations to persistent breast pain may be considerable., Implications for Cancer Survivors: Where persistent pain occurs, referral for the management of pain and, where appropriate, lymphedema is warranted.

Background: This study examined pregnancy-associated breast cancer (PABC) and pregnancy following treatment for breast cancer., Methods: We analysed data from a questionnaire-based, prospective study of women diagnosed with breast cancer. Timing of diagnosis in relation to pregnancy was self-reported in the enrolment questionnaire. Women reported subsequent pregnancies in annual follow-up questionnaires, up to at least 5 years from diagnosis., Results: Women with PABC made up 3.3% of women <48 years at diagnosis and 14.3% of women aged <35 years at diagnosis. Nine of 46 (19.6%) women who were aged <40 years at diagnosis, and had either no children, or only one child, became pregnant subsequent to their diagnosis, and 8 experienced a live birth., Discussion: As the number of women with PABC was small, conclusions from this study are limited. However, young women should be alert to PABC, especially in the post-partum period. Some women, with incomplete families at diagnosis, are choosing to have one or more pregnancies following treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this work was to study the incidence and prevalence of self-reported lymphedema in breast cancer survivors between 2 and 4 years following diagnosis, the factors associated with the development of lymphedema and the impact of lymphedema on psychological well-being., Methods: We assessed self-reported lymphedema in the BUPA Health Foundation Health and Wellbeing After Breast Cancer Study, a questionnaire-based study of 1,683 women newly diagnosed with their first episode of invasive breast cancer in Victoria, Australia. Psychological well-being was assessed using the Psychological General Well-being Index., Results: Two years after diagnosis, nearly 20 % of women reported lymphedema and this proportion remained above 18 % 2 years later. However, self-reported lymphedema was a dynamic phenomenon, with the condition resolving in some women and others reporting onset for the first time up to 4 years from diagnosis. Lymphedema 2 years from diagnosis was positively associated with the number of nodes removed at initial surgery, although this variable only explained a small proportion of the likelihood of reporting lymphedema. The presence of lymphedema was associated with lower psychological general well-being., Conclusions: Lymphedema after breast cancer treatment frequently has a dynamic pattern and may emerge as an issue for women several years after their initial treatment. It is associated with a lower level of general well-being.

Objective: Oral adjuvant endocrine therapy (OAET) substantially improves the survival of women with hormone receptor-positive (HR) breast cancer. However, we reported previously that at 3 to 4 years after diagnosis, 18% of affected women are not using OAET primarily because of estrogen deficiency symptoms. The aim of this study was to determine the use of OAET in women with HR breast cancer 5 to 6 years from diagnosis., Methods: Analysis was carried out using data from the Bupa Health Foundation's Health and Wellbeing After Breast Cancer Study, a cohort study of 1,683 women with breast cancer who were recruited in Victoria, Australia between 2004 and 2006. All women completed an enrollment questionnaire within 12 months of diagnosis and an annual follow-up questionnaire (FQ) for 5 years. The fifth FQ was completed 5.7 years from the time of diagnosis. Use of OAET was self-reported in response to a series of questions., Results: A minimal exposure to OAET of at least 5 years (OAET in all six FQs) was reported by 19.7% of the women (n = 212), and another 46.7% (n = 503) received a minimal exposure of at least 4 years (OAET in five questionnaires). In total, 82.1% (n = 883) of the women would have received at least 3 years of treatment (OAET in at least four questionnaires). Only 7.8% (n = 84) reported never using OAET., Conclusions: Most women with HR breast cancer who survive at least 5 years have persisted with OAET despite the adverse effects of estrogen depletion.

Background: For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years., Methods: In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633., Findings: Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%)., Interpretation: For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis., Funding: Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.

Background: There is no evidence of benefit in terms of survival or quality of life for intensive surveillance of women with early breast cancer (BC) and current guidelines reflect this. We have examined whether Victorian women, nearly 4 years from a diagnosis of localized BC, were being managed according to these guidelines., Methods: Participants are women in the BUPA Health Foundation Health and Wellbeing after Breast Cancer prospective cohort study. All participants completed an enrolment questionnaire within 12 months of diagnosis and then completed follow-up questionnaires every 12 months thereafter. In the third follow-up questionnaire, completed nearly 4 years from the time of diagnosis, women were asked about imaging tests they had in the previous 12 months., Results: The analysis was completed on 673 women who were stage 1 at the time of diagnosis and had not reported evidence of recurrence or a new BC since diagnosis. Of the 673, 603 (89.5%) reported having had a mammogram in the previous 12 months and 319 (52.9% of those having a mammogram) reported a breast ultrasound. Seventy-one per cent of women reported no other imaging investigations in the previous 12 months., Conclusions: Our study shows that, nearly 4 years from diagnosis, Australian practitioners are generally adhering to guidelines about imaging surveillance of BC survivors. Practitioners could use the guidelines for the education of BC survivors about appropriate health surveillance., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Objective: The aim of this study was to investigate the extent of discontinuation of oral adjuvant endocrine therapy (OAET) in women nearly 4 years from the diagnosis of their first episode of invasive breast cancer and the reasons for such discontinuation., Methods: We used a large, prospective cohort study of women who had been diagnosed with their first episode of invasive breast cancer between 2004 and 2006, recruited through a state-based cancer registry. All participants completed an enrollment questionnaire (EQ) within 12 months of diagnosis and annual follow-up questionnaires (FQs) thereafter. The data in this report were obtained from the EQ and the first three FQs., Results: A total of 1,370 women with hormone receptor-positive disease completed the EQ. At the completion of the third FQ nearly 4 years from diagnosis, 1,193 women remained in the study. Use of OAET peaked by 2 years postdiagnosis. At nearly 4 years from diagnosis, 18% of the 1,193 women remaining in the study were not taking OAET. Of these women, just more than half had ceased therapy mainly owing to a range of adverse effects, predominantly estrogen deficiency symptoms, but the remainder (8% of women remaining in the study) had never used OAET., Conclusions: Our study confirms that early discontinuation of OAET due to estrogen deficiency symptoms remains an important issue despite calls for strategies to address this problem. The number of women potentially suitable for OAET but not receiving it was almost as great as the number of those who have discontinued therapy.

Objective: To explore the beliefs held by breast cancer (BC) survivors about the factors that contribute to the development of their BC.  , Methods: The BUPA Health Foundation Health and Well-being after Breast Cancer Study is a prospective cohort study of 1684 women recruited within 12 months of their first diagnosis with invasive BC. Participants completed an enrollment questionnaire (EQ), first follow-up questionnaire (FQ1) and a second follow-up questionnaire (FQ2), 12 months and 24 months post-EQ, respectively. In the FQ2, women were asked whether they believed anything contributed to the development of their BC and whether they had made lifestyle changes since the FQ1. Well-being was assessed at the FQ2 using the psychological general well-being index (PGWB).  , Results: In total, 1496/1684 women completed the FQ2 and 43.5% reported belief in a factor that may have contributed to their developing BC. These women were more likely to be younger (p<0.0001) and educated beyond high school (p<0.0001). Stress (58.1%) was the most common reason given, followed by previous use of hormone therapy (17.0%) and a family history of any cancer (9.8%). Women who believed stress contributed to their BC had lower PGWB scores than other study participants (70.9 ± 16.1, n = 361 versus 77.3 ± 14.9, n = 1071, mean difference = 6.4, 95% CI: 4.6-8.2 p<0.0001) and were more likely to have made lifestyle changes since their BC diagnosis.  , Conclusions: Many women with BC believe that stress has contributed to their condition. Women who held this belief were more likely to adopt strategies to reduce stress than those who did not., (Copyright © 2011 John Wiley & Sons, Ltd.)

Purpose: Smoking and alcohol consumption after breast cancer diagnosis have received little attention. The aim of this study was to describe the change in smoking and alcohol consumption of women in the BUPA Health Foundation Health and Wellbeing After Breast Cancer Study in the first 2 years after diagnosis., Methods: We documented cigarette and alcohol use at diagnosis in a prospective cohort study of 1,588 Australian women with invasive breast cancer in an enrolment questionnaire and again 2 years later (follow-up questionnaire, FQ1)., Results: Twelve percent of participants smoked at diagnosis. Nearly one third of these had quit by FQ1 and of those continuing, 1 in 4 were smoking fewer cigarettes per day. Smoking more at diagnosis was significantly associated with smoking at FQ1.Over 70% of women reported consuming alcohol in each questionnaire. The proportion of women consuming more than four alcoholic drinks per occasion at least weekly dropped between the time of diagnosis and FQ1, although by FQ1, 1 in 12 women still reported this drinking pattern., Conclusions: Smoking and alcohol consumption are important health issues for women with breast cancer. Health care providers should consider using evidence-based interventions to reduce smoking and drinking in this group.

Introduction: Breast cancer (BC) remains the most common non-skin cancer in women and an increasing number are living as BC survivors., Aim: The aim of this article is to evaluate the impact of the first diagnosis of invasive BC and its treatment, menopausal symptoms, and body image on sexual function., Methods: The BUPA Foundation Health and Wellbeing after Breast Cancer Study is a prospective cohort study of 1,684 women recruited within 12 months of their first diagnosis with invasive BC. Each participant completed an enrollment questionnaire (EQ) and first follow-up questionnaire (FQ1) 12 months post-EQ., Main Outcome Measure: Sexual function was evaluated by the Menopause-Specific Quality of Life Questionnaire embedded within the FQ1., Results: Of the 1,011 women in the analyses, 70% experienced sexual function problems and 77% reported vasomotor symptoms. Women experiencing sexual function problems were postmenopausal (P = 0.02), experienced vasomotor symptoms (P < 0.01), and used aromatase inhibitors (P = 0.03). Women with vasomotor symptoms were twice as likely to experience sexual function problems (odds ratio [OR] 1.93, 95% confidence interval [CI] 141, 2.63; P < 0.001). This association was more extreme for women on aromatase inhibitors (OR 3.49, 95% CI 1.72, 7.09; P = 0.001) but did not persist in women not using endocrine therapies (OR 1.41, 95% CI 0.84, 2.36; P = 0.19). Women on aromatase inhibitors were more likely to report sexual function problems (OR 1.50, 95% CI 1.0, 2.2, P = 0.04) and women with body image issues were 2.5 times more likely to report sexual function problems (OR 2.5 95% CI 1.6, 3.7, P < 0.001). Women using tamoxifen were not more likely to experience sexual function problems (OR 1.1, 95% CI 0.8, 1.5, P = 0.6); however, women with body image issues were twice as likely to experience sexual function problems (OR 2.1, 95% CI 1.5, 3.0, P < 0.001)., Conclusion: Seventy percent of partnered BC survivors less than 70 experienced sexual function problems. Sexual problems are related to the use of aromatase inhibitors which can exacerbate menopausal symptoms., (© 2010 International Society for Sexual Medicine.)

Objective: Our aim was to document patterns of consultation with alternative practitioners, use of complementary and alternative medicine (CAM) commonly used to alleviate menopausal symptoms, and lifestyle changes made by women in the first 2 years after their diagnosis with invasive breast cancer., Methods: A total of 1,588 women in the MBF Foundation Health and Wellbeing After Breast Cancer Study completed both the enrollment questionnaire and the first follow-up questionnaire (FQ1), on average, 41 and 92 weeks after diagnosis, respectively. The Menopause Quality of Life Questionnaire and the Psychological General Wellbeing Index were included in the FQ1. Logistic regression analysis was used to examine characteristics associated with consulting a CAM practitioner or using CAMs., Results: At the time of completion of the FQ1, 16.4% of women had consulted a CAM practitioner and 10.6% reported using at least one CAM commonly used to alleviate menopausal symptoms. Women who consulted a CAM practitioner and women who were using at least one CAM at the time of completion of the FQ1 were, on average, younger and more educated and had a higher Menopause Quality of Life Questionnaire score than did women who did not. Of the women, 33.6% reported having made a dietary change, and the most common lifestyle change was an increase in physical activity, which was reported by 29.0% of women., Conclusions: The frequency of use of CAMs in common usage for menopausal symptoms by women with breast cancer was lower than anticipated, increased with time from diagnosis, and is associated with more severe menopausal symptoms.

Purpose: The aim of this study was to document the psychological well-being of a group of women with invasive breast cancer (BC) on an average of nearly 2 years after their diagnosis., Methods: Participants were women in the Medical Benefits Fund Australia Limited Foundation Health and Wellbeing after Breast Cancer Study, a cohort study of 1,684 women recruited within 12 months of their diagnosis with invasive BC, who completed their first annual follow-up questionnaire. Psychological well-being was measured using the Psychological General Well Being Index questionnaire (PGWB) in women with BC., Results: The PGWB questionnaire was completed by 1,589 women on an average of 92 weeks after their BC diagnosis, of whom 46 had evidence of active disease. PGWB total scores for all age groups of the BC cohort were lower than community-based norms (p < 0.001 for age groups > or =70, 60-<70, 50-60; p = 0.002 for age group 40-<50 and p = 0.05 for age group <40). PGWB total scores for the BC cohort were positively associated with age (p < 0.001) and living with others (p < 0.01) and inversely associated with active disease (p < 0.001) and education beyond secondary school (p = 0.03). For the domain of anxiety, there was no statistically significant association with living with others but an inverse association with education beyond school., Conclusion: A higher level of education may be associated with increased anxiety and lower well-being. Social support is particularly important for women with BC who are known to live alone.

Exposure to postmenopausal hormone therapy (HT) may affect the stage, histological type, and hormone receptor (HR) status of invasive breast cancer at the time of diagnosis. One thousand six hundred eighty-four women with newly diagnosed first invasive breast cancer were recruited to the "MBF Foundation Health and Wellbeing after Breast Cancer Study." Women using systemic HT estrogen (E) or E combined with progesterone (P) at the time of diagnosis of breast cancer were compared with those not using HT. Breast cancer tumor data were obtained from the Victorian Cancer Registry. Regression analysis was used to determine the associations between HT use or not at the time of diagnosis and tumor histology (ductal vs lobular), stage (I vs II, III, IV), HR status (ER+ or PR+ or both vs ER- or PR-). Of 1,377 women included in the analysis, 226 (16%) were using HT at the time of diagnosis. Of HT users, 20.4% had lobular breast cancer, 50% were stage I, and 85.8% had HR-positive tumors. Of non-users, 13.6% had lobular breast cancer, 48.2% were stage I, and 82.4% had HR-positive tumors. Use of systemic HT was associated with increased odds of having lobular compared with ductal breast cancer (OR = 1.75, 95% CI = 1.14-2.69, p = 0.01). There were no associations between HT use and either breast cancer stage or HR status. Women using systemic HT at the time of diagnosis were more likely to have lobular rather than ductal breast cancer compared with women not on HT.

Objective: The aim of this study was to investigate the level of understanding in women with newly diagnosed invasive breast cancer of the key clinical features of their disease that are important determinants in treatment decision making., Methods: The 1684 women aged between 26 and 88 years at diagnosis enrolled in a 5-year cohort study were asked by questionnaire about their estrogen receptor (ER) and progesterone receptor (PR) status and about their past or current treatment with adjuvant endocrine therapy. Information was linked with their ER and PR status determined from the histopathology report. Logistic regression analysis was used to explore the relationship between age and education status and the likelihood of being able to correctly report hormone receptor status, as well as the relationship between the likelihood of receiving adjuvant endocrine therapy and knowledge of hormone receptor status in women who were ER or PR positive., Results: Not being able to correctly report hormone receptor status was associated with being older and having a lower level of education. Of women who were ER positive or PR positive or both and were at least 40 weeks from diagnosis, having received some form of endocrine therapy was significantly associated with self-identification as being ER or PR positive (OR=1.82, 95% CI 1.24-2.68, p=0.002), even when age was taken into account., Conclusions: That self-knowledge of hormone receptor status was independently associated with likelihood of receiving endocrine therapy suggests that the methods of helping women understand the nature of their breast cancer are worthy of review.

Introduction: Although the efficacy of testosterone for the treatment of hypoactive sexual desire disorder is well established, the effect of testosterone therapy on breast cancer risk remains uncertain., Aim: The incidence of invasive breast cancer among past and current testosterone users., Methods: Retrospective cohort study of 631 women ever treated with testosterone between January 1989 and December 2007 in a clinical endocrinology practice., Main Outcome Measure: The incidence of invasive breast cancer since first exposure, and the standardized incidence rate ratio (IRR) calculated using Australian age-specific incidence rates for 2005., Results: The mean age of the women at first exposure to testosterone therapy was 49.1 +/- 8.2 years, median treatment duration, 1.3 years, and mean follow-up of 6.7 +/- 4.6 years, providing 4,015 woman-years of follow-up. Twelve cases of invasive breast cancer occurred among 599 women breast cancer-free before treatment, giving an age adjusted IRR of 1.35 (95% confidence interval 0.76-2.38). There was no evidence of an independent effect of duration of exposure on breast cancer risk., Conclusion: In this study, testosterone use was not associated with a significant increase in breast cancer risk.

Aim: To document the prevalence of family history of breast cancer (BC) amongst women newly-diagnosed with invasive BC and to explore the relationship between family history and cancer size and stage., Methods: A cross-sectional analysis was conducted on baseline questionnaire data from a cohort study of 1,684 women diagnosed with invasive BC within the previous 12 months and recruited between 2004 and 2006 in Victoria, Australia., Results: Women with affected first degree relative(s) were more likely to have a smaller BC (odds ratio for

Objective: The aim of this article was to describe a pragmatic approach to the menopausal status classification of clinical research study participants that allows for women who have gynecological circumstances that mask their natural menstrual pattern., Design: We demonstrate the application of an algorithm for the Health and Wellbeing After Breast Cancer study based on self-reported menstrual cycle pattern, gynecological history, presence or absence of vasomotor symptoms, and systemic hormone use to classify women with newly diagnosed breast cancer as premenopausal, perimenopausal, or postmenopausal for research purposes., Results: Within 12 months of their breast cancer diagnosis, 1,684 participants, mean +/- SD age 57.4 +/- 11.9 years, completed a comprehensive women's health questionnaire. Menopausal status in 71.8% of the women was classified by reported bilateral oophorectomy, age, greater than 12 months of amenorrhea, or regular menstrual cycles and absence of symptoms. Status in the remainder was classified by progression through the decision tree., Conclusions: The Health and Wellbeing After Breast Cancer study menopausal classification algorithm is a useful tool for research involving female participants that allows for the classification of women who have had a hysterectomy and/or use systemic hormonal contraception or hormone therapy.

Background: Breast cancer (BC) mortality is declining such that the number of survivors of BC in the community is increasing. BC survivors report a range of sequelae from their cancer and its management beyond the period of their immediate treatment. Previous studies to document these have generally been small, clinic-based or commenced years after diagnosis. We have recruited a large cohort of women newly diagnosed with invasive BC from the community who will be followed for five years in order to systematically document the physical, psychological and socio-economic consequences of BC and its treatment. The aim of this manuscript is to describe the issues encountered in the recruitment of this community-based study population., Methods: Women residing in the southern Australian state of Victoria newly diagnosed with invasive BC were recruited to this cohort study using two approaches: directly from the community using an advertising campaign and contemporaneously using an invitation to participate from the Victorian Cancer Registry (VCR)., Results: Over the two and half year recruitment period, 2135 women were recruited and agreed to receive the enrollment questionnaire (EQ). Of these, 1684 women were eligible and completed an EQ, with the majority of participants having been recruited through the VCR (n = 1321). Only 16% of women contacted by the VCR actively refused participation following a letter of invitation and phone follow-up. The age distribution and tumour characteristics of participants are consistent with state-wide data and their residential postcodes include 400 of a possible 699. Recruitment through a direct community awareness program aimed at women with newly diagnosed invasive BC was difficult, labour-intensive and expensive. Barriers to the recruitment process were identified., Conclusion: Most of the women in this study were recruited through a state-based cancer registry. Limitations to recruitment occurred because we required questionnaires to be completed within 12 months of diagnosis in a setting where there is several months delay in notification of new cases to the Registry. Characteristics of the cohort suggest that it is generally representative of women in the state of Victoria newly diagnosed with BC.

Background: Testosterone therapy is being increasingly used in the management of postmenopausal women. However, as clinical trials have demonstrated a significantly increased risk of breast cancer with oral combined estrogen-progestin therapy, there is a need to ascertain the risk of including testosterone in such regimens., Objective: Evaluation of experimental and epidemiological studies pertaining to the role of testosterone in breast cancer., Design: Literature review., Setting: The Jean Hailes Foundation, Research Unit., Main Outcome Measures: Mammary epithelial proliferation, apoptosis and breast cancer., Results: In experimental studies, testosterone action is anti-proliferative and pro-apoptotic, and mediated via the AR, despite the potential for testosterone to be aromatized to estrogen. Animal studies suggest that testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer promoting effects of estrogen on mammary epithelium. In premenopausal women, elevated testosterone is not associated with greater breast cancer risk. The risk of breast cancer is also not increased in women with polycystic ovary syndrome who have chronic estrogen exposure and androgen excess. However, in postmenopausal women, who are oestrogen deplete and have increased adipose aromatase activity, higher testosterone has been associated with greater breast cancer risk., Conclusion: Available data indicate the inclusion of testosterone in estrogen-progestin regimens has the potential to ameliorate the stimulating effects of hormones on the breast. However, testosterone therapy alone cannot be recommended for estrogen deplete women because of the potential risk of enhanced aromatisation to estrogen in this setting.

Androgens have important physiological effects in women. Postmenopausal androgen replacement, most commonly as testosterone therapy, is becoming increasingly widespread. This is despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety data. With respect to the breast specifically, there is the potential for exogenous testosterone to exert either androgenic or indirect estrogenic actions, with the latter potentially increasing breast cancer risk. In experimental studies, androgens exhibit growth-inhibitory and apoptotic effects in some, but not all, breast cancer cell lines. Differing effects between cell lines appear to be due primarily to variations in concentrations of specific coregulatory proteins at the receptor level. In rodent breast cancer models, androgen action is antiproliferative and proapoptotic, and is mediated via the androgen receptor, despite the potential for testosterone and dehydroepiandrosterone to be aromatized to estrogen. The results from studies in rhesus monkeys suggest that testosterone may serve as a natural endogenous protector of the breast and limit mitogenic and cancer-promoting effects of estrogen on mammary epithelium. Epidemiological studies have significant methodological limitations and provide inconclusive results. The strongest data for exogenous testosterone therapy comes from primate studies. Based on such simulations, inclusion of testosterone in postmenopausal estrogen-progestin regimens has the potential to ameliorate the stimulating effects of combined estrogen-progestin on the breast. Research addressing this is warranted; however, the number of women that would be required for an adequately powered randomized controlled trial renders such a study unlikely.