Comparing Prognosis for BRCA1, BRCA2, and Non-BRCA Breast Cancer.

BACKGROUND: Germline pathogenic variants (PV) in BRCA1 and BRCA2 genes, which account for 20% of familial breast cancer (BC) cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome. Previous studies, mostly including higher numbers of BRCA1 BC patients, yielded conflicting results regarding BRCA1/2 BC outcomes. In the Portuguese population, BRCA2 BC is diagnosed more frequently than BRCA1 BC. We aimed to compare clinicopathological characteristics and prognosis between BC patients with BRCA1 and BRCA2 mutations and a control group without germline PV (BRCA-wt). Furthermore, we explored the frequency and outcomes of risk-reducing surgeries in BRCA-mutated patients. METHODS: Prospective follow-up was proposed for patients with a diagnosed BRCA1/2 PV. For this study, a matched control group (by age at diagnosis, by decade, and by stage at diagnosis) included BC patients without germline PV. We compared overall survival (OS) and invasive disease-free survival (iDFS) within the three groups, and the use of risk-reducing surgeries among the BRCA cohort. RESULTS: For a mean follow-up time of 113.0 months, BRCA-wt patients showed longer time to recurrence (p = 0.002) and longer OS (p < 0.001). Among patients with BRCA mutations, no statistical differences were found, although patients with BRCA2 BC had longer iDFS and OS. Uptake of risk-reducing surgeries (contralateral prophylactic mastectomy and salpingo-oophorectomy) were negative predictors of invasive disease and death, respectively. CONCLUSIONS: Testing positive for a BRCA PV is associated with a higher risk of relapse and death in patients with BC in the Portuguese population. Risk-reducing mastectomy and salpingo-oophorectomy were associated with lower incidence of relapse and longer median iDFS and OS, respectively.

Is There a Role for Risk-Reducing Bilateral Breast Surgery in BRCA1/2 Ovarian Cancer Survivors? An Observational Study.

BACKGROUND: Risk-reducing surgeries are an option for cancer risk management in BRCA1/2 individuals. However, while adnexectomy is commonly recommended in breast cancer (BC) survivors, risk-reducing bilateral breast surgery (RRBBS) is controversial in ovarian cancer (OC) survivors due to relapse rates and mortality. METHODS: We conducted a retrospective analysis of BRCA1/2-OC survivors, with OC as first cancer diagnosis. RESULTS: Median age at OC diagnosis for the 69 BRCA1/2-OC survivors was 54 years. Median overall survival was 8 years, being significantly higher for BRCA2 patients than for BRCA1 patients (p = 0.011). Nine patients (13.2%) developed BC at a median age of 61 years. The mean overall BC-free survival was 15.5 years (median not reached). Eight patients (11.8%) underwent bilateral mastectomy (5 simultaneous with BC treatment; 3 RRBBS) at a median age of 56.5 years. The median time from OC to bilateral mastectomy/RRBBS was 5.5 years. CONCLUSIONS: This study adds evidence regarding a lower BC risk after BRCA1/2-OC and higher survival for BRCA2-OC patients. A comprehensive analysis of the competing risks of OC mortality and recurrence against the risk of BC should be individually addressed. Surgical BC risk management may be considered for longer BRCA1/2-OC disease-free survivors. Ultimately, these decisions should always be tailored to patients' characteristics and preferences.

International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer-Specific Health-Related Quality-of-Life Questionnaire.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. METHODS AND MATERIALS: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. RESULTS: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. CONCLUSIONS: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.

Hereditary breast cancer and ancestry in the Madeira archipelago: an exploratory study.

Access to genetic testing and counselling in remote areas such as the Madeira archipelago, in the Northern Atlantic Ocean, may be complex. Different counselling methods, including telegenetics, should be explored. In this study, we characterise the Hereditary Breast/Ovarian Cancer (HBOC) families with Madeira ancestry enrolled in our programme. Of a total of 3,566 index patients tested between January 2000 and June 2018, 68 had Madeira ancestry and 22 were diagnosed with a pathogenic germline variant (PV). As in the whole group, BRCA2 PV were more frequent in Madeira patients (68.4%: c.9382C>T (26.3%), c.658_659del (21%), c.156_157insAlu (10.5%), c.793+1G>A (5.3%) and c.298A>T (5.3%). However, the most frequently diagnosed PV in Madeira patients was the BRCA1 c.3331_3334del (31.6%). BRCA1/2 detection rates were 27.9% and 10.5% for Madeira and the whole group, respectively. This study is the first characterisation of HBOC patients with Madeira ancestry. A distinct pattern of BRCA1/2 variants was observed, and the geographic clustering of BRCA1 c.3331_3334del variant may support the possibility of a founder mutation previously described in Northern Portugal. The high detection rate observed reinforces the need to reduce gaps in access to genetic testing in Madeira and other remote areas. According to current guidelines, timely identification of HBOC patients can contribute to their ongoing care and treatment.

Low rectal cancer treatment strategies: a cohort study assessing watch and wait.

PURPOSE: Treatment strategies for low rectal cancer have been evolving toward achieving less treatment morbidity with the same oncological success-we aimed to assess the results of the new watch and wait (W&W) strategy in our cohort. METHODS: A tertiary care cohort study was conducted. New patients with rectal adenocarcinoma up to 6 cm from the anal margin, cM0, locally staged higher than cT1N0, evaluated between November 2014 and October 2018, were included. All 93 patients received neoadjuvant radiotherapy ± chemotherapy. Re-evaluation was planned 8-12 weeks after the end of treatment. Patients showing clinical complete response (cCR) were given the choice of either to proceed to surgery or to enter W&W. RESULTS: Of the 93 patients, 82.8% were re-evaluated and 20.8% had cCR. Patients in clinical stages II/III were significantly less likely to achieve cCR than those in stage I (p = 0.017). After a mean follow-up of 17.44 months, there were 4 regrowths in the 16 patients under W&W, all submitted to R0 surgery, ypN0; there were no deaths or local recurrences; one patient with regrowth had distant recurrence. Sixty patients underwent direct surgery after a mean follow-up of 16.23 months; 3 patients had local and distant recurrences; 7 others had only distant recurrences; there were 8 deaths. There were no statistically significant differences between patients under W&W and patients who underwent direct surgery regarding local or distant recurrences, or death (p > 0.9; p = 0.44; p = 0.19, respectively). CONCLUSION: The W&W strategy for low rectal cancer achieved the same oncological outcomes as the traditional strategy while sparing some patients from surgery.

Febrile neutropenia in FEC-D regimen for early stage breast cancer: is there a place for G-CSF primary prophylaxis?

BACKGROUND: Breast cancer clinical trials prove better outcomes for anthracycline-taxane regimes albeit of a higher hematologic toxicity. Original trials may under-estimate febrile neutropenia (FN) event rates. OBJECTIVE: To describe the occurrence of FN events related to FEC-D for breast cancer treatment in the real-life setting. METHODS: Retrospective analysis of 189 patients with non-metastatic breast cancer consecutively treated with FEC-D (3 cycles of 5-FU, Epirubicin and Cyclophosphamide followed by 3 cycles of Docetaxel) at our Center during 33 months. FN and related dose delay and reduction, regimen change, G-CSF prophylaxis and hospitalization were analyzed. RESULTS: Fifty-one patients (27%) developed at least one episode of FN during FEC-D, 21% during Docetaxel cycles. There were 61 (5.6%) FN episodes in 1100 cycles of FEC-D administered, 77% occurred during Docetaxel cycles (46% on the first D cycle). G-CSF was used in 5.8% of cycles. Hospital admission needed in 54.1% of FN events, 16.4% prompted dose reduction and 23% next cycle delay. There were no FN related deaths. CONCLUSIONS: G-CSF prophylaxis is recommended for chemotherapy regimens associated with a FN rate higher than 20%. Based on our FN rates, we now recommend primary G-CSF prophylaxis during the administration of cycles 4 to 6 in FEC-D.

Rectal cancer management in elderly patients: experience of a single Portuguese institution.

BACKGROUND: The incidence of rectal cancer increases with age, and older patients are more likely to have other chronic conditions that can affect outcome and tolerability of treatment. OBJECTIVE: The incidence of rectal cancer increases with age, and older patients are more likely to have other chronic conditions that can affect outcome and tolerability of treatment. METHODS: 59 patients aged 75 years and older with stage II-III rectal cancer who were treated during a 3-year period were included in the study. Comorbidities were assessed using the Charlson Comorbidity Index (CCI) and the patients were divided into 2 groups based on their CCI scores: Fit (score of 0-1 points) and Vulnerable (score of greater than or = 2). Primary endpoint was survival at 1 and 3 years. RESULTS: The sample included 43 patients (72.9%) in the Fit group and 16 patients (27.1%) in the Vulnerable group. The most common comorbidities were myocardial infarction, diabetes, and chronic lung disease. One-year survival the same between the groups (P = .330), but 3-year survival was lower in the Vulnerable group patients (83.7% vs 56.3%, respectively; P = .040). The rates of neoadjuvant chemo- and radiotherapy use and low anterior resection performance were the same between the groups. Colostomy closure was achieved more frequently in the Fit group compared with the Vulnerable group (83.3% vs 55.6%; P = .083). There was no difference in mean disease-free survival, grade 3-4 toxicity, and dose reduction between the groups. CONCLUSIONS: Comorbidity assessment should always be included in standard oncological management of elderly patients. Fit patients can be managed with standard treatment and may bene¦t from a conventional, more aggressive approach in their therapy.

Anorectal malignant melanoma: retrospective analysis of management and outcome in a single Portuguese Institution.

Anorectal melanoma is an uncommon cancer with a poor prognosis. We aim to describe the clinical presentation, treatment and outcome of patients with anorectal melanoma in our center. Retrospective study of patients with anorectal melanoma treated between 2000 and 2011 at a cancer center in Lisbon. Ten patients were identified, eight females and two males, with median age 70.5 years (32-79). Symptoms at presentation were rectal bleeding (8), anal pain (4) and discomfort (3). Tumor location was anal (6), rectal (3) and anorectal transition (2). Seven patients had surgery: abdomino-pelvic resection (5) and local resection (2). Among the two patients who underwent local resection, one was an incidental finding in a hemorrhoidectomy specimen. This patient had further adjuvant chemotherapy (dacarbazine). Three patients had distant metastasis at diagnosis, one had chemotherapy and two had best supportive care. Six of the seven operated patients relapsed in a median time of 5.4 months: distant metastasis (4), local recurrence (1), both (1). The two local relapse patients had surgical widening of resection margins (1) and radiotherapy (2). One-year survival was 30 %; 3-year survival was 20 %. Anorectal melanoma has a poor prognosis due to advanced disease at presentation and aggressive course, with relapse in almost all operated patients. Treatment guidelines have not been established due to the lack of randomized studies. However, recent studies show that sphincter-sparing surgical procedures along with low dose intensity radiotherapy seem to achieve a local control similar to abdomino-pelvic resection. No systemic therapy is considered standard of care for advanced disease, and regimens are extrapolated from cutaneous melanoma experience.