Brita Arver

Psychological Reactions, Quality of Life, and Body Image After Bilateral Prophylactic Mastectomy in Women At High Risk for Breast Cancer: A Prospective 1-Year Follow-Up Study

PURPOSEnTo prospectively evaluate body image, sexuality, emotional reactions (anxiety, depression), and quality of life in a sample of women having increased risk for breast cancer before and 6 months and 1 year after bilateral prophylactic mastectomy (BPM), and to compare preoperative expectations of the operation with postoperative reactions concerning the impact on six areas of the womens lives.nnnPATIENTS AND METHODSnA total of 90 of 98 consecutive women who underwent BPM during October 1997 to December 2005 were included. Data were collected by self-administered questionnaires (eg, Hospital Anxiety and Depression scale, Swedish Short Term-36 Health Survey, Body Image Scale, Sexual Activity Questionnaire) before the operation (n = 81), and 6 (n = 71) and 12 months (n = 65) after BPM.nnnRESULTSnAnxiety decreased over time (P = .0004). No corresponding difference was found for depression. No differences in health-related quality of life over time were found, with one exception. A substantial proportion of the women reported problems with body image 1 year after BPM (eg, self consciousness, 48%; feeling less sexually attractive, 48%; and dissatisfaction with the scars, 44%). Sexual pleasure was rated lower 1-year post-BPM as compared with before operation (P = .005), but no differences over time in habit, discomfort, or activity were found.nnnCONCLUSIONnNo negative effects on anxiety, depression, and quality of life were found. Anxiety and social activities improved. Negative impact on sexuality and body image was reported.

Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers

Importance The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. Objectives To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. Design, Setting, and Participants Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. Exposures BRCA1/2 mutations, family cancer history, and mutation location. Main Outcomes and Measures Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. Results Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). Conclusions and Relevance These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.

Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: Results from the International BRCA1/2 carrier cohort study

Background: Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated in a small number of studies. Methods: We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox proportional hazards framework. Results: There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had ever used OC were at a significantly reduced risk of developing ovarian cancer (hazard ratio, 0.52; 95% confidence intervals, 0.37-0.73; P = 0.0002) and increasing duration of OC use was associated with a reduced ovarian cancer risk (P trend = 0.0004). The protective effect of OC use for BRCA1 mutation carriers seemed to be greater among more recent users. Tubal ligation was associated with a reduced risk of ovarian cancer for BRCA1 carriers (hazard ratio, 0.42; 95% confidence intervals, 0.22-0.80; P = 0.008). The number of ovarian cancer cases in BRCA2 mutation carriers was too small to draw definitive conclusions. Conclusions: The results provide further confirmation that OC use, number of full-term pregnancies, and tubal ligation are associated with ovarian cancer risk in BRCA1 carriers to a similar relative extent as in the general population. (Cancer Epidemiol Biomarkers Prev 2009;18(2):601–10)

Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland

In the Finnish breast and ovarian cancer families six BRCA1 and five BRCA2 mutations have been found recurrently. Some of these recurrent mutations have also been seen elsewhere in the world, while others are exclusively of Finnish origin. A haplotype analysis of 26xa0Finnish families carrying a BRCA1 mutation and 20xa0families with a BRCA2 mutation indicated that the carriers of each recurrent mutation have common ancestors. The common ancestors were estimated to trace back to 7–36xa0generations (150–800xa0years). The time estimates and the geographical clustering of these founder mutations in Finland are in concordance with the population history of this country. Analysis of the cancer phenotypes showed differential ovarian cancer expression in families carrying mutations in the 5′ and 3′ ends of the BRCA1 gene, and earlier age of ovarian cancer onset in families with BRCA1 mutations compared with families with BRCA2 mutations. The identification of prominent and regional BRCA1 and BRCA2 founder mutations in Finland will have significant impact on diagnostics in Finnish breast and ovarian cancer families. An isolated population with known history and multiple local founder effects in multigenic disease may offer distinct advantages also for mapping novel predisposing genes.

Preoperative MRI of the Breast (POMB) Influences Primary Treatment in Breast Cancer: A Prospective, Randomized, Multicenter Study

BackgroundBreast magnetic resonance imaging (MRI) has shown high sensitivity in determining tumor extent, multifocality, and occult contralateral breast cancer. Low specificity, unnecessary mastectomies, and costs are arguments against MRI. The purpose of this study was to determine whether preoperative breast MRI would affect primary surgical management, reduce reexcision/reoperation procedures, and influence the choice of neoadjuvant treatment in patients with newly diagnosed breast cancer.MethodsThis prospective, randomized, multicenter study included 440 breast cancer patients younger than aged 56xa0years from three, Swedish, large-volume breast units. Patients were randomly allocated on a 1:1 basis to either preoperative staging with breast MRI (nxa0=xa0220) or no breast MRI (nxa0=xa0220) (control group). Treatment planning of all patients was discussed at multidisciplinary team conferences.ResultsIn patients randomized to the MRI group, who had an observed higher percentage of planned breast-conserving surgeryxa0(BCS) compared with the control group, a change from suggested breast conservation to mastectomy occurred in 23 of 153 (15xa0%) patients. Breast MRI provided additional information in 83 of 220 (38xa0%) patients, which caused a change in treatment plan in 40 (18xa0%). The breast reoperation rate was significantly lower in the MRI group: 11 of 220 (5xa0%) versus 33 of 220 (15xa0%) in the control group (pxa0<xa00.001). The number of mastectomies, axillary reoperations, and the number of patients receiving neoadjuvant chemotherapy after definitive treatment did not differ significantly between the groups.ConclusionsPreoperative staging with breast MRI in women younger than age 56xa0years altered the treatment plan in 18xa0% of the patients. Although a higher MRI-related conversion rate from breast conservation to mastectomy was found, the final numbers of mastectomies did not differ between the two groups. The breast reoperation rate in the MRI group was significantly reduced.

Bilateral prophylactic mastectomy in Swedish women at high risk of breast cancer: a national survey.

Background/Objective:This study attempted a national inventory of all bilateral prophylactic mastectomies performed in Sweden between 1995 and 2005 in high-risk women without a previous breast malignancy. The primary aim was to investigate the breast cancer incidence after surgery. Secondary aims were to describe the preoperative risk assessment, operation techniques, complications, histopathological findings, and regional differences. Methods:Geneticists, oncologists and surgeons performing prophylactic breast surgery were asked to identify all women eligible for inclusion in their region. The medical records were reviewed in each region and the data were analyzed centrally. The BOADICEA risk assessment model was used to calculate the number of expected/prevented breast cancers during the follow-up period. Results:A total of 223 women operated on in 8 hospitals were identified. During a mean follow-up of 6.6 years, no primary breast cancer was observed compared with 12 expected cases. However, 1 woman succumbed 9 years post mastectomy to widespread adenocarcinoma of uncertain origin. Median age at operation was 40 years. A total of 58% were BRCA1/2 mutation carriers. All but 3 women underwent breast reconstruction, 208 with implants and 12 with autologous tissue. Four small, unifocal, invasive cancers and 4 ductal carcinoma in situ were found in the mastectomy specimens. The incidence of nonbreast related complications was low (3%). Implant loss due to infection/necrosis occurred in 21 women (10%) but a majority received a new implant later. In total, 64% of the women underwent at least 1unanticipated secondary operation. Conclusions:Bilateral prophylactic mastectomy is safe and efficacious in reducing future breast cancer in asymptomatic women at high risk. Unanticipated reoperations are common. Given the small number of patients centralization seems justified.

Contralateral prophylactic mastectomy in breast cancer patients with a family history: A prospective 2-years follow-up study of health related quality of life, sexuality and body image

INTRODUCTIONnContralateral prophylactic mastectomy (CPM) is the most effective option to prevent the occurrence of a second breast cancer in hereditary breast cancer patients. This study aimed to prospectively evaluate health-related quality of life (HRQoL), anxiety and depression, sexuality and body image in breast cancer patients with a family history undergoing CPM with immediate breast reconstruction.nnnPATIENTS AND METHODSnIn total, 60 of 69 eligible patients agreed to participate in the study. Four validated questionnaires were used: the SF-36, the Hospital Anxiety and Depression Scale (HAD), the Body Image Scale (BIS), and the Sexual Activity Questionnaire (SAQ). Forty-five patients (75%) responded before CPM, 49 (82%) at 6 months, and 45 (75%) at 2 years after CPM.nnnRESULTSnOverall, the patients showed a satisfactory HRQoL 2 years after CPM, similar to women in the general population. There were no differences in HRQoL, anxiety, depression or sexuality before and after CPM. However, more than half of the women reported at least one body image problem 2 years postoperatively.nnnCONCLUSIONnNo adverse effects on HRQoL, anxiety, depression or sexuality were observed. However, some aspects of body image were negatively affected after CPM. These findings could be used in preoperative counselling of breast cancer patients opting for CPM.

High satisfaction rate ten years after bilateral prophylactic mastectomy - a longitudinal study.

Women from families with an increased risk for breast/ovarian cancer have undergone bilateral prophylactic mastectomy (BPM) since the early 1990s at the Karolinska University Hospital in Sweden. Perceptions of BPM as reported by the first women who underwent the procedure have previously been evaluated on a short-term basis (1-3 years). The present study aims to evaluate the long-term (10 years) physical and psychological consequences of BPM in the same cohort of women. Some of the very first women to undergo BPM participated in the present interview study (n= 13). The semi-structured interviews focused on the womens long-term experiences related to BPM and immediate breast reconstruction. Overall, the women were satisfied with their decision to undergo BPM and perceived a negligible remaining risk of getting breast cancer. For most women, the operation had not resulted in changes in family life or lifestyle (n= 8), although some described that the relationship with their spouse was affected (8/13), either in a negative (n= 5) or positive (n= 3) way. The cosmetic results were mainly positive (n= 10). Recurrent counselling and support during the whole process of decision, treatment and follow up is recommended.

Technical aspects and outcome after prophylactic mastectomy and immediate breast reconstruction in 30 consecutive high-risk patients.

&NA; The purpose of this study was to evaluate a consecutive series of patients operated on with prophylactic mastectomy and immediate breast reconstruction with implants, focusing on preoperative assessment, technical aspects of surgical outcome, and number of postoperative complications on a short‐term basis. Thirty consecutive healthy women with an increased risk of breast cancer who were therefore operated on with bilateral prophylactic mastectomy and immediate breast reconstruction are reported. A multidisciplinary approach with a geneticist, general surgeon, plastic surgeon, specially trained nurse, psychologist, gynecologist, and oncologist was used preoperatively, with thorough information provided to the patient about the surgery. Eleven patients had gene mutations, and in all patients, the geneticist had performed a risk assessment. The mean age of the patients was 41 years. The technique was modified over time with smaller or special incisions and tailor‐made adjustments for each patient. Great care was taken to remove all breast tissue. The tops of the breast nipples were regrafted for cosmetic purposes, and the base was sent for histopathologic examination. In most cases, permanent expander prostheses with detachable valves were used. The areolas were tattooed, if they were not left in place. No patient had occult cancer or carcinoma in situ. Four postoperative complications occurred, including two hematomas, one infection (treated with antibioties). and one pneumothorax in a patient with severe asthma. All reconstructions were fulfilled. The mean hospital stay was 5.7 days. The time from mastectomy to the final tattooing of the areolas was 260 days. All patients returned to normal daily activities after fulfilled reconstruction.

BRCA2 germline mutations in Swedish breast cancer families

Mutations in the breast cancer susceptibility gene (BRCA2) are believed to be responsible for a significant fraction of hereditary breast cancer. To determine the BRCA2 mutation spectrum in a subset of Swedish breast cancer families, 162 families were screened for germline mutations in this gene. A combination of RT-PCR, PTT and direct DNA sequencing was used. Two mutations and one previously reported polymorphic variant resulting in a truncated protein were identified. Our data suggest that only a small proportion of Swedish breast cancer families is attributable to BRCA2 germline mutations. This result, in combination with the low frequency of BRCA1 germline mutations identified in our previous study, suggests additional high penetrant as well as low penetrant breast cancer susceptibility genes are involved in familial breast cancer.