Acceptability and Adherence in a Chemoprevention Trial among Women at Increased Risk for Breast Cancer Attending the Modena Familial Breast and Ovarian Cancer Center (Italy)

Chemoprevention for women at risk for breast cancer has been shown to be effective, but in actual practice, women's uptake of chemoprevention has been poor. We explored factors that influence acceptability, adherence, and dropout in the International Breast (Prevention) Intervention Study during our first 3 years of activity at the Modena Familial Breast and Ovarian Cancer Center. We evaluated socio-demographic characteristics, health status, adherence, and side effect intensity. Semi-structured interviews analyzed reasons for accepting/refusing/stopping the trial. A total of 471 postmenopausal women were invited to participate, of which 319 declined to participate (68%), 137 accepted to participate (29%), and 15 participants did not make a final decision (3%). Breast cancer-related worries and trust in our preventive and surveillance programs were the most frequent reasons for accepting. Side effect-related worry was the most frequent reason for refusing. General practitioners' and family members' opinions played an important role in the decision-making process. Adherence significantly decreased after a 12-month follow-up, but it remained unchanged after 24- and 36-month follow-ups. Mild/moderate side effects reported by women did not change after 12 months of treatment. Forty percent of women withdrew from the study due to complaints of side effects. We concluded that chemoprevention trials are difficult medical experiments and that the process of deciding about whether or not to participate is based mainly on beliefs and values. This study has important clinical implications. During counselling with prospective participants, it is important to emphasize the potential benefits and to promote an informed choice. How participants make decisions, their belief systems, and their perception of risk are all factors that should be investigated in future research

Male Bilateral Risk-Reducing Mastectomy: Report of a Case

Male prophylactic mastectomy is described only in sporadic cases and always performed in men with BRCA mutation with a contralateral breast cancer diagnosis. This case may suggest that we need to tailor counseling and decision‐making process for males carrying BRCA mutation and take into consideration risk‐reduction surgery when wished and strongly motivated by the consultant or in the presence of multiple risk factors in addition to gene mutation

Development and Validation of an Italian Adaptation of the Psychosocial Aspects of Hereditary Cancer Questionnaire

Individuals that attend cancer genetic counseling may experience test-related psychosocial problems that deserve clinical attention. In order to provide a reliable and valid first-line screening tool for these issues, Eijzenga and coworkers developed the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire. The aim of this work was to develop an Italian adaptation of the PAHC (I-PACH). This prospective multicenter observational study included three stages: (1) development of a provisional version of the I-PAHC; (2) pilot studies aimed at testing item readability and revising the questionnaire; and (3) a main study aimed at testing the reliability and validity of the final version of the I-PAHC with the administration of a battery comprising measures of depression, anxiety, worry, stress, and life problems to 271 counselees from four cancer genetic clinics. Adapting the original PAHC to the Italian context involved adding two further domains and expanding the emotions domain to include positive emotions. While most of the items were found to be easy to understand and score, some required revision to improve comprehensibility; others were considered irrelevant or redundant and therefore deleted. The final version showed adequate reliability and validity. The I-PAHC provides comprehensive content coverage of cancer genetic-specific psychosocial problems, is well accepted by counselees, and can be considered a sound assessment tool for psychosocial issues related to cancer genetic counseling and risk assessment in Italy

The impact of reproductive life on breast cancer risk in women with family history or BRCA mutation

Reproductive history and exogenous hormonal exposures are acknowledged risk factors for breast cancer in the general population. In women at increased breast cancer risk for genetic predisposition or positive family history, data regarding these risk factors are limited or con icting, and recommendations for these categories are unclear. We evaluated the characteristics of reproductive life in 2522 women at increased genetic or familial breast cancer risk attending our Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely to be hormone receptor negative, diagnosed at 35 years or before and multiple during the lifetime than tumors in women at increased familial risk, while the distribution of invasive cancers and HER2 positive tumors was similar in the different risk groups. At least one full- term pregnancy (HR 0.27; 95% CI 0.12\u20130.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09\u20130.66; p = 0.005) or more (HR 0.25; 95% IC 0.08\u20130.82; p = 0.022) than one year and late age at menopause (HR 0.10; 95% CI 0.01\u20130.82; p = 0.033) showed to be protective factors in BRCA mutation carriers, while in women at increased familial risk early age at rst full-term pregnancy (HR 0.62; 95% IC 0.38\u20130.99; p = 0.048) and late menarche (HR 0.61; 95% CI 0.42\u20130.85; p = 0.004) showed to be the main protective factors. Finally, for the entire population, combined hormonal contraceptives demonstrated to do not increase breast cancer risk. The results of our study suggest that women at high familial risk and mutation carries develop tumors with different clinical-pathological characteristics and, consequently, are in uenced by different protective and risk factors

Hereditary pancreatic cancer: A retrospective single-center study of 5143 Italian families with history of BRCA-related malignancies

The identification of BRCA mutations plays a crucial role in the management of hereditary cancer prevention and treatment. Nonetheless, BRCA-testing in pancreatic cancer (PC) patients is not universally introduced in clinical practice. A retrospective analysis was conducted, firstly, to evaluate the rate of BRCA-positive families among those presenting a family history of PC besides breast and/or ovarian cancer. Secondly, the relationship between BRCA pathogenic variants and PC risk was evaluated. Finally, the characteristics of PC developed in BRCA families were described. Among 5143 family trees reporting breast and/or ovarian cancer cases, 392 showed a family history of PC. A total of 35 families (24.5% selected by the Modena Criteria and 21.3% by the NCCN Criteria) were positive to BRCA testing. Among the BRCA1 mutations, 36.8% were found within a region defined by c.3239\u2013c.3917, whilst 43.7% of BRCA2 mutations were located within c.7180\u2013c.8248. This study confirmed that an increase in the rate of positive tests in families with PC when associated to breast and/or ovarian tumors. Moreover, this analysis indicated two possible Pancreatic Cancer Cluster Regions that should be verified in future research. Finally, PC in families with breast and/or ovarian cancer history, particularly in BRCA families, were diagnosed at younger age and showed better one-year overall survival

Impact of Genetic Counseling in Women with a Family History of Breast Cancer in Italy

As the impact of breast cancer (BC) risk assessment in asymptomatic women with a family history of BC had never been explored in Italy, we performed a study on a retrospective series of women who had undergone BC risk assessment. To this aim, a semi-structured telephone interview was administered to 82 women. Most participants considered the information received as clear (96.2 %) and helpful (76.8 %). Thirty-eight (46.3 %) stated that their perceived risk of BC had changed after the counseling: for 40.2 % it had decreased, for 6.1 % increased; however, women highly overestimating their risk at the baseline (≥4-fold) failed to show improvements in risk perception accuracy. Sixty-six women (80.5 %) stated they had followed the recommended surveillance, while 19.5 % had not, mainly due to difficulties in arranging examinations. Most women (89.0 %) had shared the information with their relatives, with 57.3 % reporting other family members had undertaken the recommended surveillance. BC risk assessment was associated with high rates of satisfaction and had a favorable impact on risk perception in a subgroup of women. The impact on surveillance adhesion extended to relatives. Organized programs for identification and surveillance may help identify a larger fraction of at-risk women and overcome the reported difficulties in arranging surveillance

Prophylactic Surgery to Reduce the Risk of Developing Breast Cancer: Issues and Clinical Implications

Women with BRCA1 or BRCA2 mutations are at increased risk of developing breast and ovarian cancer. Options to manage this risk are regular surveillance, chemoprevention, and risk reduction surgery which includes, risk reduction mastectomy (bilateral or contralateral) and risk reduction salpingo-oophorectomy. Risk-reduction surgery (RRS) has been proven to be efficacy in the reduction of breast and ovarian cancer up to 90% but are irreversible procedure and psychological and physical implication could be challenging for women. Authors provide an overview of the current literature regarding efficacy of RRS, acceptability and psychological implication. Decisions about RRS are complex owing to the multiple associated risks and benefits. Specific and multidisciplinary approach is needed. Many factors, mostly psychological, influenced the decision. Research on psychological impact of these procedure are controversial. The majority of these studies reported that women who choose surgery have diminished anxiety about cancer risk, and experience few psychological difficulties, but physical complication and change in body image, sexual life are often reported. In conclusion, women need to be counselled about the decision to undergo RRS Potential negative effects of should be discussed thoroughly with each woman considering this procedure. Careful psychological follow up after the surgery should be scheduled

Acceptability and adherence in a chemoprevention trial among women at increased risk for breast cancer attending the Modena Familial Breast and Ovarian Cancer Center

Chemoprevention for women at risk for breast cancer has been shown to be effective, but in actual practice, women's uptake of chemoprevention has been poor. We explored factors that influence acceptability, adherence, and dropout in the International Breast (Prevention) Intervention Study during our first 3 years of activity at the Modena Familial Breast and Ovarian Cancer Center. We evaluated socio-demographic characteristics, health status, adherence, and side effect intensity. Semi-structured interviews analyzed reasons for accepting/refusing/stopping the trial. A total of 471 postmenopausal women were invited to participate, of which 319 declined to participate (68%), 137 accepted to participate (29%), and 15 participants did not make a final decision (3%). Breast cancer-related worries and trust in our preventive and surveillance programs were the most frequent reasons for accepting. Side effect-related worry was the most frequent reason for refusing. General practitioners' and family members' opinions played an important role in the decision-making process. Adherence significantly decreased after a 12-month follow-up, but it remained unchanged after 24- and 36-month follow-ups. Mild/moderate side effects reported by women did not change after 12 months of treatment. Forty percent of women withdrew from the study due to complaints of side effects. We concluded that chemoprevention trials are difficult medical experiments and that the process of deciding about whether or not to participate is based mainly on beliefs and values. This study has important clinical implications. During counselling with prospective participants, it is important to emphasize the potential benefits and to promote an informed choice. How participants make decisions, their belief systems, and their perception of risk are all factors that should be investigated in future research

CHIRURGIA PROFILATTICA DELLA MAMMELLA NELLE PAZIENTI PORTATRICI DI MUTAZIONE DEL GENE BRCA 1/2. PERCORSO DIAGNOSTICO-TERAPEUTICO.

Le donne portatrici di una mutazione del gene BRCA1 o BRCA2 presentano un alto rischio di sviluppare un carcinoma mammario ed ovarico nel corso della vita. Le opzioni per controllare o ridurre questo rischio sono una sorveglianza clinico-strumentale regolare, la chemioprevenzione, la chirurgia \u201crisk reducing\u201d (mastectomia bilaterale o controlaterale) e la salpingo-ooforectomia. La Chirurgia presenta una riduzione del rischio di insorgenza del carcinoma mammario ed ovarico fino al 90-95%, ma \ue8 una procedura irreversibile con implicazioni fisiche e psicologiche importanti per le donne interessate. Gli Autori riportano l\u2019esperienza in tema di tumori ereditari della mammella sottolineando l\u2019importanza di allestire un team multidisciplinare dedicato nel cui ambito sia disponibile un \u201ccounseling onco-genetico\u201d specifico e la necessit\ue0 di allestire un consenso informato adeguato a questa problematica

A rapid genetic counselling and testing in newly diagnosed breast cancer is associated with high rate of risk-reducing mastectomy in BRCA1/2-positive italian women

BACKGROUND: Risk-reducing mastectomy (RRM) decreases breast cancer (BC) risk in BRCA1/2 mutation carriers by up to 95%, but the Italian attitude towards this procedure is reluctant. PATIENTS AND METHODS: This is an observational study with retrospective design, using quantitative and qualitative research methods, aimed at evaluating the attitude towards RRM by rapid genetic counselling and testing (RGCT), at the time of BC diagnosis, compared with traditional genetic counselling and testing (TGCT), after previous BC surgery. Secondary aims were to investigate patient satisfaction after RRM and the rate of occult tumour in healthy breasts. A total of 1168 patients were evaluated: 1058 received TGCT, whereas 110 underwent RGCT. RESULTS: In TGCT, among 1058 patients, 209 (19.7%) mutation carriers were identified, with the rate of RRM being 4.7% (10 of 209). Conversely in RGCT, among 110 patients, 36 resulted positive, of which, 15 (41.7%) underwent bilateral mastectomy at the BC surgery time, showing an overall good satisfaction, measured by interpretative phenomenological analysis 12 months after the intervention. CONCLUSIONS: Our study shows that RGCT in patients with a hereditary profile is associated with a high rate of RRM at the BC surgery time, this being the pathway offered within a multidisciplinary organization. KEYWORDS: BRCA1/2 mutation carriers; acceptability; genetic counselling; risk-reducing mastectom