Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial.

BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. INTERPRETATION: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.

Mammography screening and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a prospective study.

Women with a genetic predisposition to breast cancer may be at increased risk of cancer after exposure to ionizing radiation. It is unclear whether mammography screening increases the risk of breast cancer among BRCA1 and BRCA2 carriers. We identified 2,346 women with a BRCA1 (n = 1844) or BRCA2 (n = 502) mutation and no breast cancer, and we reviewed their history of mammography exposure. These women were followed for an average of 5.3 years and were observed for new breast cancer diagnoses. At study entry, 1808 women (77.1 %) reported ever having had a mammogram; of these, 204 women (11.2 %) reported having had a mammogram before age 30. We estimated the hazard ratios for the development of invasive breast cancer, conditional on the number of prior mammograms and on the age at first mammogram. Hazard ratios were estimated and stratified by gene (BRCA1 or BRCA2), relative to women with no exposure. We observed no significant association between prior mammography exposure and breast cancer risk for BRCA1 carriers (HR 0.79; 95 % CI 0.53-1.19; P = 0.26) or for BRCA2 carriers (HR 0.90; 95 % CI 0.35-2.34; P = 0.83). An early age at first mammogram (<30 years) did not increase breast cancer risk among BRCA1 carriers (HR 0.75; 95 % CI 0.41-1.37; P = 0.35) or among BRCA2 carriers (HR 0.69; 95 % CI 0.19-2.48; P = 0.57). Exposure to mammography in women with BRCA1 and BRCA2 mutations is not associated with an increased risk of breast cancer.

Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers.

It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.

Duration of tamoxifen use and the risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.

Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80 %. Tamoxifen treatment of the first cancer has been associated with a reduction in the risk of a subsequent contralateral cancer. We studied 1,504 women with a known BRCA1 or BRCA2 mutation, 411 women with bilateral breast cancer (cases) and 1,093 women with unilateral breast cancer (controls) in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of first breast cancer as the cases. For each woman who used tamoxifen, the starting and stopping dates were abstracted and the duration of tamoxifen use was calculated. Three hundred and thirty-one women had used tamoxifen (22 %); of these 84 (25 %) had completed four or more years of tamoxifen, the remainder stopped prematurely or were current users. For women with up to 1 year of tamoxifen use, the odds ratio for contralateral breast cancer was 0.37 (95 % CI 0.20-0.69; p = 0.001) compared to women with no tamoxifen use. Among women with 1-4 years of tamoxifen use the odds ratio was 0.53 (95 % CI 0.32-0.87; p = 0.01). Among women with four or more years of tamoxifen use the odds ratio was 0.83 (95 % CI 0.44-1.55; p = 0.55). Short-term use of tamoxifen for chemoprevention in BRCA1 and BRCA2 mutation carriers may be as effective as a conventional 5-year course of treatment.

Changing communication needs and preferences across the cancer care trajectory: insights from the patient perspective.

PURPOSE: In this program of research, we sought to expand our understanding of how cancer patients' communication needs and preferences change across the course of their illness trajectory. To address known limitations in the empirical knowledge base, we designed a study capitalizing on representative patient reports as they occurred within time and across experience obtaining care for this disease. METHODS: We used a longitudinal cohort design informed by interpretive description methodology to follow 125 patients over a multi-year period as they reflected on their ongoing experiences with cancer care communication. RESULTS: In relation to each phase of their cancer care trajectory, patients identified tension points and contextual challenges impinging on what they felt constituted helpful and unhelpful patient-provider communication. CONCLUSIONS: Findings from this study create a dynamic portrait of how we can better inform communication approaches and interventions through interpretations of population knowledge and individual experience.

Should all BRCA1 mutation carriers with stage I breast cancer receive chemotherapy?

To estimate the 15-year survival following a diagnosis of stage I breast cancer among women who carry a BRCA1 mutation and to determine predictors of mortality, including the use of chemotherapy. Patients were 379 women with stage I breast cancer for whom a BRCA1 mutation had been identified, in herself or in a close family member. Patients were followed for up to 15 years from the initial diagnosis of breast cancer. Survival rates were estimated for women by age, tumor size (≤ 1 cm; > 1 cm), ER status (±), and by chemotherapy (yes/no). 42 women died of breast cancer in the follow-up period (11.2 %). Survival rates were similar for women with cancers of size 0-1.0 cm and size 1.1-2.0 cm. Of the 267 women in the study who used chemotherapy, 21 had died (7.9 %) compared to 21 deaths among 112 women who did not receive chemotherapy (18.8 %; p = 0.002). The 15-year survival was 89.4 % for women who received chemotherapy and was 73.1 % for women who did not receive chemotherapy (p = 0.08; log rank). The adjusted hazard ratio for death following a diagnosis of stage I breast cancer associated with chemotherapy was 0.53 (95 % CI 0.28-1.07; p value 0.06) after adjusting for age of diagnosis, tumor size, and estrogen receptor status. This was statistically significant only among women with ER-negative breast cancers (HR = 0.28; 95 % CI 0.10-0.79; p = 0.02). BRCA1 positive women who are treated for stage I breast cancer with chemotherapy have better survival than those who do not receive chemotherapy. The difference cannot be explained by other prognostic factors. All women with invasive breast cancer and a BRCA1 mutation should be considered to be candidates for chemotherapy.

The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation.

Physicians are often approached by young women with a BRCA mutation and a recent history of breast cancer who wish to have a baby. They wish to know if pregnancy impacts upon their future risks of cancer recurrence and survival. To date, there is little information on the survival experience of women who carry a mutation in one of the BRCA genes and who become pregnant. From an international multi-center cohort study of 12,084 women with a BRCA1 or BRCA2 mutation, we identified 128 case subjects who were diagnosed with breast cancer while pregnant or who became pregnant after a diagnosis of breast cancer. These women were age-matched to 269 mutation carriers with breast cancer who did not become pregnant (controls). Subjects were followed from the date of breast cancer diagnosis until the date of last follow-up or death from breast cancer. The Kaplan-Meier method was used to estimate 15-year survival rates. The hazard ratio for survival associated with pregnancy was calculated using a left-truncated Cox proportional hazard model, adjusting for other prognostic factors. Among women who were diagnosed with breast cancer when pregnant or who became pregnant thereafter, the 15-year survival rate was 91.5 %, compared to a survival of 88.6 % for women who did not become pregnant (adjusted hazard ratio = 0.76; 95 % CI 0.31-1.91; p = 0.56). Pregnancy concurrent with or after a diagnosis of breast cancer does not appear to adversely affect survival among BRCA1/2 mutation carriers.

International rates of breast reconstruction after prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Breast reconstruction is an option for women with BRCA1 or BRCA2 mutations who elect to undergo prophylactic mastectomy to prevent breast cancer. We report on the uptake of breast reconstruction after prophylactic mastectomy in women with BRCA mutations from eight countries. METHODS: Women with a BRCA1 or BRCA2 mutation were questioned regarding their cancer preventive practices. Information was recorded on prophylactic mastectomy and breast reconstruction. RESULTS: A total of 1,635 women with a BRCA1 or BRCA2 mutation who elected to undergo prophylactic mastectomy from eight countries were included. A total of 1,137 women (69.5%) had breast reconstruction after prophylactic mastectomy. A total of 58.7% of women over the age of 45 years at the time of prophylactic mastectomy had breast reconstruction compared to 77.6% of women 35 years of age or younger [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.26-0.50, p < 0.001]. In addition, 62.9% of women with a breast cancer diagnosis (contralateral prophylactic mastectomy) had breast reconstruction after prophylactic mastectomy compared to 79.7% of women without a previous breast cancer diagnosis (OR 0.48, 95% CI 0.38-0.61, p < 0.001). A total of 66.9% of women from Canada had breast reconstruction after mastectomy compared to 71.9% of American women (OR 0.75, 95% CI 0.59-0.96, p = 0.02). CONCLUSIONS: The majority of women elect for breast reconstruction after prophylactic mastectomy. However, younger women and those without a previous diagnosis of breast cancer are more likely to have breast reconstruction than older women or those with a previous diagnosis of cancer.

Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation carriers.

BACKGROUND: Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting. METHODS: We constructed a Markov model of annual MRI and mammography screening for BRCA1/2 carriers, using local data and published values. We calculated cost-effectiveness as cost per quality-adjusted life-year gained (QALY), and conducted one-way and probabilistic sensitivity analysis. RESULTS: The incremental cost-effectiveness ratio (ICER) of annual mammography plus MRI screening, compared to annual mammography alone, was $50,900/QALY. After incorporating parameter uncertainty, MRI screening is expected to be a cost-effective option 86% of the time at a willingness-to-pay of $100,000/QALY, and 53% of the time at a willingness-to-pay of $50,000/QALY. The model is highly sensitive to the cost of MRI; as the cost is increased from $200 to $700 per scan, the ICER ranges from $37,100/QALY to $133,000/QALY. CONCLUSIONS: The cost-effectiveness of using MRI and mammography in combination to screen for breast cancer in BRCA1/2 mutation carriers is finely balanced. The sensitivity of the results to the cost of the MRI screen itself warrants consideration: in jurisdictions with higher MRI costs, screening may not be a cost-effective use of resources, but improving the efficiency of MRI screening will also improve cost-effectiveness.

The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: an international prospective cohort study.

OBJECTIVE: To evaluate the risk of endometrial cancer in women who carry a mutation in the BRCA1 or the BRCA2 gene. METHODS: We followed 4456 women with a BRCA1 or a BRCA2 mutation for incident cases of endometrial cancer. The incidence of endometrial cancer was estimated per 100,000 women per year. The hazard ratios for endometrial cancer were estimated by calculating standardized incidence ratios (SIRs) according to age group and country of residence. We estimated the impact of tamoxifen and hormone replacement therapy on the incidence of endometrial cancer in BRCA1 and BRCA2 carriers. RESULTS: After a mean follow-up of 5.7 years, we identified 17 endometrial cancers (13 cases in BRCA1 and 4 cases in BRCA2). The SIR for BRCA1 carriers was 1.91 (95% CI: 1.06-3.19, p=0.03) and for BRCA2 carriers was 1.75 (95% CI: 0.55-4.23, p=0.2). The SIR was 4.14 (95% CI: 1.92 to 7.87) for women who received tamoxifen and was 1.67 (95% CI: 0.81 to 3.07) for women who did not receive tamoxifen. The ten-year cumulative risk of endometrial cancer in women who were treated with tamoxifen was 2.0%. CONCLUSIONS: The risk of endometrial cancer is higher in BRCA1 mutation carriers than in the general population. The excessive risk is largely attributable to a history of tamoxifen use, but the actual risk of endometrial cancer associated with tamoxifen is small. It is important to discuss hysterectomy at the time of prophylactic bilateral salpingo-oophorectomy if tamoxifen is to be considered.

Outcome of patients with biochemical recurrence of prostate cancer after PSMA PET/CT-directed radiotherapy or surgery without systemic therapy.

BACKGROUND: Radiotherapy (RT) and surgery are potential treatment options in patients with biochemical recurrence (BCR) following primary prostate cancer treatment. This study examines the value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-informed surgery and RT in patients with BCR treated without systemic therapy. METHODS: This is a post-hoc subgroup analysis of a prospective clinical trial. Inclusion criteria were: histologically proven prostate cancer at initial curative-intent treatment, BCR after primary treatment with curative intent, having five or fewer lesions identified on [18F]DCFPyL PET/CT, and treatment with either PET/CT-directed RT or surgery without systemic therapy. The biochemical progression-free survival after PSMA ligand PET/CT-directed RT and surgery was determined. Uni- and multivariate Cox regression analyses were performed for the association of patients' characteristics, tumor-specific variables, and PSMA PET/CT imaging results with biochemical progression at the last follow-up. RESULTS: Fifty-eight patients (30 in surgery and 28 in radiotherapy groups) met the inclusion criteria. A total of 87 PSMA-positive lesions were detected: 16 local recurrences (18.4%), 54 regional lymph nodes (62.1%), 6 distant lymph nodes (6,8%), and 11 osseous lesions (12.7%). A total of 85.7% (24 of 28) and 70.0% (21 of 30) of patients showed a ≥ 50% decrease in prostate-specific antigen (PSA) levels after RT and surgery, respectively. At a median follow-up time of 21 months (range, 6-32 months), the median biochemical progression-free survival was 19 months (range, 4 to 23 months) in the radiotherapy group, as compared with 16.5 months (range, 4 to 28 months) in the surgery group. On multivariate Cox regression analysis, the number of PSMA positive lesions (2-5 lesions compared to one lesion), and the anatomic location of the detected lesions (distant metastasis vs. local relapse and pelvic nodal relapse) significantly correlated with biochemical progression at the last follow-up, whereas other clinical, tumor-specific, and imaging parameters did not. CONCLUSIONS: This study suggests that RT or surgery based on [18F]DCFPyL PET/CT are associated with high PSA response rates. The number and site of lesions detected on the PSMA PET/CT were predictive of biochemical progression on follow-up. Further studies are needed to assess the impact of targeting these sites on patient relevant outcomes. TRIAL REGISTRATION: Registered September 14, 2016; NCT02899312; https://clinicaltrials.gov/ct2/show/NCT02899312.

Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

INTRODUCTION: Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers. METHODS: We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer. RESULTS: Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43). CONCLUSIONS: These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.

The risk of breast cancer in women with a BRCA1 mutation from North America and Poland.

Women with a BRCA1 mutation face a high lifetime risk of breast cancer. It is unknown to what extent environmental factors modify the inherent genetic risk. If women from different countries, but with similar mutations, experience different levels of cancer risk, nongenetic risk modifiers are likely to be present. Study subjects were a cohort of 1477 women with a BRCA1 mutation, from Canada (n = 358), the United States (n = 256) and Poland (n = 863). The women were followed for a mean of 4.3 years and 130 incident cases of breast cancer were recorded. Annual cancer incidence rates were calculated, and based on these, penetrance curves were constructed for women from North America and Poland. In a Cox proportional hazards model, residence in Poland, versus North America, was associated with an adjusted hazard ratio of 0.54 (95% CI 0.34-0.86; p = 0.01). The risk of breast cancer to age 70 was estimated to be 49% for women from Poland and 72% for women from North America. Among women with BRCA1 mutations, the risk of breast cancer in women who reside in Poland is less than that of women who reside in North America. The reasons for the difference are unknown, but this observation suggests that environmental factors or genetic modifiers are important in determining risk.

Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers.

Women with a BRCA1 or BRCA2 mutation have an elevated risk of breast cancer and of contralateral breast cancer. In this study, we estimate the risk of non-synchronous ipsilateral breast cancer after a diagnosis of breast cancer in BRCA carriers and evaluate the effects of various treatments on this risk. Patients were 396 women with stage I or stage II breast cancer with an intact ipsilateral breast and for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until the first of ipsilateral mastectomy, ipsilateral breast cancer, death or last follow-up. The 5-year actuarial risk of ipsilateral breast cancer was 5.8% (95% CI 3.2-8.4%) and the 10-year risk was 12.9% (95% CI 8.7-17.1%). Subjects who received chemotherapy had a significantly lower risk of ipsilateral breast cancer compared to those who did not receive chemotherapy (RR 0.45; 95% CI 0.24-0.84; P = 0.01). Radiotherapy was associated with a reduced risk of ipsilateral breast cancer (RR 0.28; 95% CI 0.12-0.63; P = 0.002). Oophorectomy was associated with a significant reduction in the risk of ipsilateral breast cancer (RR 0.33; 95% CI; 0.13-0.81; P = 0.02). On average, following a diagnosis of breast cancer, the annual risk of ipsilateral breast cancer risk in BRCA mutation carriers is 1.2% per year. For women treated with chemotherapy, radiation therapy or oophorectomy the risk is low, compared to women who did not receive any of these treatments.

Women's constructions of the 'right time' to consider decisions about risk-reducing mastectomy and risk-reducing oophorectomy.

BACKGROUND: Women who are notified they carry a BRCA1/2 mutation are presented with surgical options to reduce their risk of breast and ovarian cancer, including risk-reducing mastectomy (RRM) and risk-reducing oophorectomy (RRO). Growing evidence suggests that a sub-group of women do not make decisions about RRM and RRO immediately following genetic testing, but rather, consider these decisions years later. Women's perspectives on the timing of these decisions are not well understood. Accordingly, the purpose of this research was to describe how women construct the 'right time' to consider decisions about RRM and RRO. METHODS: In-depth interviews were conducted with 22 BRCA1/2 carrier women and analyzed using qualitative, constant comparative methods. RESULTS: The time that lapsed between receipt of genetic test results and receipt of RRM or RRO ranged from three months to nine years. The findings highlighted the importance of considering decisions about RRM and RRO one at a time. The women constructed the 'right time' to consider these decisions to be when: (1) decisions fit into their lives, (2) they had enough time to think about decisions, (3) they were ready emotionally to deal with the decisions and the consequences, (4) all the issues and conflicts were sorted out, (5) there were better options available, and (6) the health care system was ready for them. CONCLUSIONS: These findings offer novel insights relevant to health care professionals who provide decision support to women considering RRM and RRO.

Patient perceptions of helpful communication in the context of advanced cancer.

AIMS AND OBJECTIVES: Based on a secondary analysis of data from a large qualitative study on cancer care communication, we address the question: what do patients with advanced cancer identify as helpful in their communication encounters with health care providers? BACKGROUND: Communication is of critical importance to the care of patients with advanced cancer. A better understanding of what such patients identify as helpful in their communication encounters with nurses and other health care providers seems critical to creating evidence-informed recommendations for best practices. DESIGN: Secondary analysis of qualitative interview data. METHODS: Data from 18 participants interviewed individually and 16 focus group participants, with advanced cancer in the palliative phase of care. Interpretive description methodology informed data collection and analysis. RESULTS: Findings suggest four key elements are critically important to consider in communications with patients in an advanced or palliative phase - respecting the importance of time, demonstrating caring, acknowledging fear and balancing hope and honesty in the provision of information. CONCLUSIONS: Communication is an important element in the provision of advanced cancer care. RELEVANCE TO CLINICAL PRACTICE: Findings emphasise the complex meanings inherent in cancer care communication and identify central themes that are fundamental to effective cancer care communication.

Smoking and the risk of breast cancer in BRCA1 and BRCA2 carriers: an update.

Among women with a mutation in BRCA1 or BRCA2, the risk of breast cancer is high, but it may be modified by exogenous and endogenous factors. There is concern that exposure to carcinogens in cigarette smoke may increase the risk of cancer in mutation carriers. We conducted a matched case-control study of 2,538 cases of breast cancer among women with a BRCA1 (n = 1,920) or a BRCA2 (n = 618) mutation. One non-affected mutation carrier control was selected for each case, matched on mutation, country of birth, and year of birth. Odds ratios were calculated using conditional logistic regression, adjusted for oral contraceptive use and parity. Ever-smoking was not associated with an increased breast cancer risk among BRCA1 carriers (OR = 1.09; 95% CI 0.95-1.24) or among BRCA2 carriers (OR = 0.81; 95% CI 0.63-1.05). The result did not differ when cases were restricted to women who completed the questionnaire within two years of diagnosis. A modest, but significant increase in risk was seen among BRCA1 carriers with a past history of smoking (OR = 1.27; 95% CI 1.06-1.50), but not among current smokers (OR = 0.95; 0.81-1.12). There appears to be no increase in the risk of breast cancer associated with current smoking in BRCA1 or BRCA2 carriers. There is a possibility of an increased risk of breast cancer among BRCA1 carriers associated with past smoking. There may be different effects of carcinogens in BRCA mutation carriers, depending upon the timing of exposure.

Patient real-time and 12-month retrospective perceptions of difficult communications in the cancer diagnostic period.

Communication is a notoriously complex challenge in the cancer care context. Our program of research involves exploration of patient-provider communications across the cancer trajectory from the patient perspective.Toward this end, we have been following a cohort of 60 cancer patients, representing a range of tumor sites, from immediately after diagnosis through to recovery, chronic, or advanced disease. Drawing on interpretive description analytic techniques, we documented patterns and themes related to various components of the cancer journey. In this article, we report on findings pertaining to poor communication during the initial diagnostic period, as described by patients at the time of diagnosis and 1 year later.These findings illuminate the dynamics of communication problems during that complex period, and depict the mechanisms by which patients sought to confront these challenges to optimize their cancer care experience. On the basis of these findings, considered in the context of the body of available evidence, suggestions are proposed as to appropriate directions for system-level solutions to the complex communication challenges within cancer care.

International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers.

Several options for cancer prevention are available for women with a BRCA1 or BRCA2 mutation, including prophylactic surgery, chemoprevention and screening. The authors report on preventive practices in women with mutations from 9 countries and examine differences in uptake according to country. Women with a BRCA1 or BRCA2 mutation were contacted after receiving their genetic test result and were questioned regarding their preventive practices. Information was recorded on prophylactic mastectomy, prophylactic oophorectomy, use of tamoxifen and screening (MRI and mammography). Two thousand six hundred seventy-seven women with a BRCA1 or BRCA2 mutation from 9 countries were included. The follow-up questionnaire was completed a mean of 3.9 years (range 1.5-10.3 years) after genetic testing. One thousand five hundred thirty-one women (57.2%) had a bilateral prophylactic oophorectomy. Of the 1,383 women without breast cancer, 248 (18.0%) had had a prophylactic bilateral mastectomy. Among those who did not have a prophylactic mastectomy, only 76 women (5.5%) took tamoxifen and 40 women (2.9%) took raloxifene for breast cancer prevention. Approximately one-half of the women at risk for breast cancer had taken no preventive option, relying solely on screening. There were large differences in the uptake of the different preventive options by country of residence. Prophylactic oophorectomy is now generally accepted by women and their physicians as a cancer preventive measure. However, only the minority of women with a BRCA1 or BRCA2 mutation opt for prophylactic mastectomy or take tamoxifen for the prevention of hereditary breast cancer. Approximately one-half of women at risk for breast cancer rely on screening alone.