A prior diagnosis of breast cancer is a risk factor for breast cancer in BRCA1 and BRCA2 carriers.

BACKGROUND: The risk of breast cancer in carriers of BRCA1 and BRCA2 mutations is influenced by factors other than the genetic mutation itself. Modifying factors include a woman's reproductive history and family history of cancer. Risk factors are more likely to be present in women with breast cancer than in women without breast cancer, and therefore the risk of cancer in the two breasts should not be independent. It is not clear to what extent modifying factors influence the risk of a first primary or a contralateral breast cancer in BRCA carriers. METHODS: We conducted a matched case-control study of breast cancer among 3920 BRCA1 or BRCA2 mutation carriers. We asked whether a past history of breast cancer in the contralateral breast was a risk factor for breast cancer. RESULTS: After adjustment for age, country of residence, and cancer treatment, a previous cancer of the right breast was found to be a significant risk factor for cancer of the left breast among BRCA1 or BRCA2 carriers (relative risk: 2.1; 95% confidence interval: 1.4 to 3.0; p < 0.0001). CONCLUSIONS: In a woman with a BRCA1 or BRCA2 mutation who is diagnosed with breast cancer, the risk of cancer in the contralateral breast depends on the first diagnosis. That observation supports the hypothesis that there are important genetic or non-genetic modifiers of cancer risk in BRCA carriers. Discovering risk modifiers might lead to greater personalization of risk assessment and management recommendations for BRCA-positive patients.

Health care provider recommendations for reducing cancer risks among women with a BRCA1 or BRCA2 mutation.

There is a significant variation in the uptake of cancer risk reducing options by women with a BRCA1 or BRCA2 mutation. It is currently unclear why these differences exist and it is possible that recommendations vary between providers and these influence patient decisions. Eligible health care providers who provide genetic counseling for hereditary breast and ovarian cancer families in Canada were identified. Each provider was asked to complete a study specific questionnaire that included their opinion of various cancer risk reduction options and their recommendations for specific cases. Respondents recommended prophylactic oophorectomy more often than prophylactic mastectomy or tamoxifen for women with a BRCA1 or BRCA2 mutation (p < 0.0001). Fewer than half of the respondents agreed with the recommendation for prophylactic mastectomy, and a minority of the respondents supported the recommendation for tamoxifen for chemoprevention. The majority of Canadian genetics health care providers adhere to the National Comprehensive Cancer Network (NCCN) Guideline of recommending prophylactic oophorectomy to mutation carriers, however, the minority of genetics health care providers recommend either prophylactic mastectomy or tamoxifen.

Incidence of colorectal cancer in BRCA1 and BRCA2 mutation carriers: results from a follow-up study.

BACKGROUND: The BRCA1 and BRCA2 genes confer increased susceptibility to breast and ovarian cancer and to a spectrum of other cancers. There is controversy regarding the risk of colorectal cancer conferred by germline mutations in these two genes. METHODS: We followed 7015 women with a BRCA mutation for new cases of colorectal cancer. Incidence rates in carriers were compared with population-specific incidence rates, and standardised incidence ratios (SIRs) were estimated. The expected numbers of cancers were computed by multiplying person-years at risk by the appropriate age-, sex- and country-specific incidence rates from the five countries. RESULTS: Twenty-one incident colorectal cancer cases were observed among all mutation carriers, compared with 23.6 cases expected. The SIR for BRCA1 carriers was 0.92 (95% confidence interval (CI), 0.54-1.40, P=0.7) and for BRCA2 carriers was 0.82 (95% CI, 0.30-1.81, P=0.7). The SIR for colon cancer was 3.81 (95% CI 1.77-7.23) for women below the age of 50 years (both genes combined) and was 0.60 (95% CI 0.33-1.00) for women aged 50 years and above. CONCLUSION: The risk of colorectal cancer is increased in female carriers of BRCA1 mutations below the age of 50 years but not in women with BRCA2 mutations or in older women.

Of Guinea pigs and gratitude: the difficult discourse of clinical trials from the cancer patient perspective.

In an ongoing longitudinal qualitative cohort study of cancer patients' needs and preferences across the cancer journey, we harvested a subset of accounts pertaining to conversations between patients and their clinicians around clinical trials. Recognising these conversations as a departure from the more routine discourses of clinical care, in that they enter into new dimensions of investment and motivation on the part of clinicians, we engaged in both secondary analysis of banked data and focussed interviewing of cancer patients to better understand how cancer patients describe communications in relation to decisions pertaining to clinical trials participation. Using constant comparative techniques informed by the interpretive description approach to applied qualitative methodology to guide a systematic analysis of this set of data, we documented patterns and themes across patient accounts. The resulting thematic depiction of clinical trials discourses from a patient perspective contrasts with assumptions apparent in the professional literature relating to the clinical advantage of trials participation, and illuminates aspects of patient-clinician interaction that are particularly amenable to disruption within this delicate and nuanced discourse. Findings from this study have implications for our understanding of the complexities of cancer communication at the delicate intersection of patient care and knowledge generation.

The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Germline mutations in BRCA1 and BRCA2 predispose to pancreatic cancer. We estimated the incidence of pancreatic cancer in a cohort of female carriers of BRCA1 and BRCA2 mutation. We also estimated survival rates in pancreatic cancer cases from families with a BRCA mutation. METHODS: We followed 5149 women with a mutation for new cases of pancreatic cancer. The standardised incidence ratios (SIR) for pancreatic cancer were calculated based on age group and country of residence. We also reviewed the pedigrees of 8140 pedigrees with a BRCA1 or a BRCA2 mutation for those with a case of pancreatic cancer. We recorded the year of diagnosis and the year of death for 351 identified cases. RESULTS: Eight incident pancreatic cancer cases were identified among all mutation carriers. The SIR for BRCA1 carriers was 2.55 (95% CI=1.03-5.31, P=0.04) and for BRCA2 carriers was 2.13 (95% CI=0.36-7.03, P=0.3). The 5-year survival rate was 5% for cases from a BRCA1 family and 4% for cases from a BRCA2 family. CONCLUSION: The risk of pancreatic cancer is approximately doubled in female BRCA carriers. The poor survival in familial pancreatic cancer underscores the need for novel anti-tumoural strategies.

Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.

PURPOSE: The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk. PATIENTS AND METHODS: Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. RESULTS: Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8%; P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36%; P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30-0.76; P=0.002). CONCLUSION: The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.

Helpful communications during the diagnostic period: an interpretive description of patient preferences.

With a diagnosis of cancer, life changes for patients in a profound manner. The window of time known as cancer diagnosis is one of considerable turbulence and distress for patients. Therefore, diagnosis constitutes a time during which communication with healthcare professionals is of particular importance in setting the stage for the way cancer illness will be experienced. Our research explores communications throughout the cancer trajectory from the perspective of patients themselves. We are following a sample of 60 cancer patients, representing a range of tumour sites, from the early diagnostic period through to recovery, chronic, or advanced disease. Using interpretive description analysis techniques, we document patterns and themes related to various components of the cancer journey. In this paper, we focus on themes related to perceived helpful communication during the diagnosis experience as reported by our study participants both at the time of being newly diagnosed patients, and as they reflect on that period 12 months later. These findings illuminate experiential issues of importance to patients in relation to cancer care communication and the manner in which helpful communications during this sensitive time may facilitate the subsequent experience living with and obtaining care for cancer.

Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation.

Genetic testing for mutations in BRCA1 and BRCA2 is available in Canada for women with a significant family history of breast cancer. For the majority of tested women, a BRCA1 or BRCA2 mutation is not found, and counselling regarding breast cancer risk is based on the review of the pedigree. In this prospective study, we estimate breast cancer risks in women with a family history of breast cancer and for whom the proband tested negative for a mutation in BRCA1 or BRCA2. Families with two or more breast cancers under the age of 50 years, or with three cases of breast cancer at any age, and who tested negative for a BRCA1 or BRCA2 mutation were identified. Follow-up information on cancer status was collected on all first-degree relatives of breast cancer cases. The standardised incidence ratios (SIRs) for breast cancer were calculated by dividing the observed numbers of breast cancer by the expected numbers of breast cancers, based on the rates in the provincial cancer registries. A total of 1492 women from 365 families were included in the analyses. The 1492 first-degree relatives of breast cancer cases contributed 9109 person-years of follow-up. Sixty-five women developed breast cancer, compared to 15.2 expected number (SIR=4.3). The SIR was highest for women under the age of 40 (SIR=14.9) years and decreased with increasing age. However, the absolute risk was higher for women between the age of 50 and 70 (1% per year) years than for women between 30 and 50 (0.4% per year) years of age. There was no elevated risk for ovarian, colon or any other form of cancer. Women with a significant family history of breast cancer (ie, two or more breast cancers under the age of 50 years, or three or more breast cancers at any age), but who test negative for BRCA mutations have approximately a four-fold risk of breast cancer. Women in these families may be candidates for tamoxifen chemoprevention and/or intensified breast screening with an MRI.

Family history as a predictor of uptake of cancer preventive procedures by women with a BRCA1 or BRCA2 mutation.

Women with a BRCA1 or BRCA2 mutation are at an elevated risk of developing breast and ovarian cancer; however, it is unclear to what extent family history influences the uptake of cancer prevention options. Women with a BRCA1/2 mutation completed a follow-up questionnaire that assessed uptake of cancer preventive options. The pedigree of each woman was reviewed, and information was recorded on cancers diagnosed in relatives. Five hundred and seventeen women were included in the study. Women with a sister with breast cancer were more likely to have a prophylactic mastectomy than those without a sister with breast cancer [odds ratios (OR) = 2.4, p = 0.003]. Uptake of prophylactic mastectomy was significantly lower in women with a mother with ovarian cancer compared with those whose mother did not have ovarian cancer (OR = 0.4, p = 0.01). Having a mother or sister with ovarian cancer significantly predicted the uptake of prophylactic oophorectomy (OR = 1.6, p = 0.04). Women with a BRCA2 mutation were less likely to have a prophylactic oophorectomy than those with a BRCA1 mutation (OR = 0.49, p = 0.0004). Among women with a BRCA1 or BRCA2 mutation, family history predicts the uptake of prophylactic mastectomy and prophylactic oophorectomy.

The effect of smoking on outcome following external radiation for localized prostate cancer.

PURPOSE: We investigated whether a smoking habit affects biochemical and survival outcome after curative external beam radiation therapy (EBRT) for localized prostate cancer. MATERIALS AND METHODS: The study population comprised 601 men treated with curative EBRT between 1994 and 1997 who had a smoking history available. Pretreatment prognostic factors were examined and high risk was defined as any of prostate specific antigen greater than 20, Gleason greater than 7 or stages T3-4. Biochemical outcome (bNED) was assessed by American Society for Therapeutic Radiology and Oncology, and Houston criteria. Biochemical, clinical, prostate cancer and nonprostate cancer death rates were examined by univariate and multivariate statistics. RESULTS: Of the men 15% were current smokers, 55% were former smokers and 31% were nonsmokers. Current smokers were younger than former smokers or nonsmokers by a mean of 2.5 years (p <0.001). Current smokers had higher risk cancers than former smokers or nonsmokers (high risk 60%, 40% and 43%, respectively, p = 0.017). Five-year bNED rates for smokers were significantly worse than for former smokers or nonsmokers (55%, 69% and 73%, p = 0.01 and 0.0019, respectively). Median followup was 59 months. Multivariate analysis confirmed smoking as an independent adverse factor for bNED (p = 0.013) even when controlling for prostate specific antigen (p <0.0001), Gleason score (p <0.0001), stage (not significant), radiation dose (not significant) and neoadjuvant hormone use (p = 0.0014). Local and metastatic failure did not differ among the groups. Prostate cancer specific mortality was nonsignificantly worse in smokers but overall mortality was much greater. CONCLUSIONS: Smokers present with higher risk prostate cancers. Outcomes following EBRT are poorer, even when accounting for differences in known pretreatment factors.

Measurement of upper extremity volume in women after axillary dissection for breast cancer.

OBJECTIVE: To determine if 2 methods of calculating upper extremity volume (using arm circumferences) can substitute for water displacement volumetry. DESIGN: Interrater and test-retest reliability and limits of agreement for volume measures. SETTING: University. PARTICIPANTS: Twenty-five women at risk for lymphedema who had undergone axillary lymph node dissection surgery for breast cancer. INTERVENTIONS: Circumference and volume measurements of both upper extremities were taken by 2 physical therapists at an initial visit and by 1 of the therapists 1 week later. MAIN OUTCOME MEASURES: Intraclass correlation coefficients (ICCs) were calculated to analyze measurement reliability. Pearson's product-moment correlation coefficient (r) was used to evaluate the relationship between volumetry and calculated truncated cone volumes. Limits of agreement were calculated to determine the level of agreement between the 2 measurement methods. RESULTS: Interrater and test-retest reliability ICCs for circumferential and volumetric data were .99 and .99, respectively. Pearson's r values were .93 and .97 for the single truncated cone and the summed truncated cone volume calculations, respectively. Limits of agreement (mean +/- 2 standard deviations) were -52 +/- 334mL and -40 +/- 234mL, respectively, between volumetry and the single truncated cone and summed truncated cone calculations. CONCLUSIONS: Calculated and volumetric measurements in this population are both reliable and closely related, but do not agree with each another, and thus should not be used interchangeably.

Radiotherapy in the treatment of dermatologic malignancies.

Although advances in surgical techniques, particularly micrographic surgery, have considerably expanded its role in the management of dermatologic malignancies, radiotherapy remains of considerable value. Its use should be considered in particular for the appropriate solid tumors in older patients, for metastatic disease, and for the more radioresponsive tumors including Merkel cell carcinoma, Kaposi's sarcoma, and the cutaneous lymphomas.

Effect of acetylsalicylic acid on radiation and cosmetic results after conservative surgery for early breast cancer: a randomized trial.

BACKGROUND AND PURPOSE: Acetylsalicylic acid (ASA) can reduce the incidence of stroke and myocardial infarction by inhibiting platelet-fibrin thrombi in small blood vessels. To determine if ASA could reduce late effects of radiation therapy mediated by damage to small blood vessels, a prospective, placebo-controlled, double-blind trial was conducted in women with early breast cancer, receiving radiotherapy to the conserved breast. MATERIALS AND METHODS: Cosmetic outcome and late radiotherapy effects were recorded prospectively for 186 women with T1 or T2, pathologically node-negative breast cancer treated with breast conservation and randomized to receive ASA (325 mg daily) or placebo for 1 year from the start of radiation therapy. Radiation was a tangent pair to the breast alone delivering a modal dose of 44 Gy in 16 daily fractions in 22-25 days. RESULTS: Median follow-up is 6.5 years. The use of ASA has not had any effect on the acute (erythema, edema or discomfort) or late (induration, telangiectasia) effects of radiotherapy (all P > 0.10), the patients' or physicians' assessment of the cosmetic outcome (all P > 0.25) or rates of breast recurrence (P > 0.25). CONCLUSION: ASA cannot be recommended to improve the outcome of radiotherapy complementing breast conserving surgery.

Late cosmetic results of short fractionation for breast conservation.

BACKGROUND AND PURPOSE: The number of fractions of radiation therapy (RT) used after breast conserving surgery varies widely and accounts for a significant proportion of the workload in a modern radiotherapy department. Internationally, 'standard' therapy ranges from 3 to 7 weeks of daily treatment with or without a boost. Short RT schedules have the attraction of reducing workload but raise concern about an increased risk of late effects and poorer cosmetic outcome. MATERIALS AND METHODS: In a randomized trial, 186 women with T1 or T2, pathologically node-negative breast cancer had cosmetic and various normal tissue effects data collected prospectively. The breast RT prescription was 44 Gy in 16 daily fractions to a tangent pair. RESULTS: Median follow-up is 6.7 years. Actuarial 5-year breast recurrence was 6%. Overall cosmetic results at 5 years were good or excellent in 89% and 96% as reported by physicians and patients, respectively, and were stable between 2 and 5 years. Breast discomfort, erythema, edema and induration were related to both surgery and RT. At 5 years, 20% had breast discomfort, 18% had induration, 6% had erythema and 3% had some degree of breast edema. Fewer patients had these effects at 5 years than immediately after primary surgery. The presence of induration prior to starting RT was associated with a greater likelihood of breast induration 3 or more years following RT (P = 0.02). Thirteen percent of patients, generally those with large breasts, developed mild inframammary telangiectasia by 5 years. CONCLUSIONS: Results are comparable to those reported from centers employing more conventional fractionation. Short fractionation produces acceptable cosmetic results for the majority of women if there are no contraindications to RT and in the absence of significant post-operative breast induration.

Postmastectomy lymphedema treated with the Wright linear pump.

Fifteen patients with postmastectomy lymphedema of the arm were treated with the Wright linear pump, a programmable, gradient pressure, sequential, intermittent compression pump. The group comprised volunteers in whom conservative measures had failed. This is a phase II trial to determine the efficacy of the pump. All patients had subjective improvement. Objectively, all showed a reduction in edema, but this was of variable degree and depended on the amount of pre-existing lymphedema in the arm. The Wright linear pump is easy to use and treatment was well tolerated. No fluid overload occurred due to treatment and no other medical problems were encountered. The Wright linear pump seems more effective than other pneumatic intermittent compression pumps available.