Purpose. This study was designed to examine the relationship between breast cancer molecular subtypes and pathological response to neoadjuvant chemotherapy (NAC)±trastuzumab, in locally advanced breast cancer (LABC). Methods. Female patients with LABC (T2T4, N0N2, and M0) who received neoadjuvant chemotherapy+trastuzumab if HER2+ subtype, followed by surgery and radiotherapy±hormonal therapy, were identified. The primary endpoint was pathologic complete response (pCR) in the breast and axilla (ypT0/ypN0), with final analysis on disease-free survival (DFS) and overall survival (OS). Results. Six hundred eighty-one patients with a median age of 44 years, premenopausal: 70, median tumour size: 7.0cm (range 411cm), stage II B: 27 and III A/III B: 73, ER+/HER2: 40.8, ER/HER2: 23, ER+/HER2+: 17.7, and ER/HER2+: 18.5. Overall pCR (ypT0/ypN0) was 23. The pCR rates based on molecular subtypes were ER+/HER2: 9; ER+/HER2+: 29; ER/HER2: 31; and ER/HER2+: 37. At median follow-up of 61 months, ER+/HER2+ and ER+/HER2 subtypes had the best 5-year DFS and OS; meanwhile, ER/HER2+ and ER/HER2 subtypes had the worst. Conclusion. Women with ER+/HER2 disease are the least likely to achieve pCR, with the highest rates in HER2+ and triple-negative subgroups. Degree of response is associated with OS; despite the comparatively higher likelihood of achieving pCR in ER/HER2+ and triple-negative, these subgroups experience a survival detriment. We are consistent with the published data that patients who attain the pathological complete response defined as ypT0/ypN0 have improved outcomes.

Sentinel lymph node biopsy in clinically detected ductal carcinoma in situ

Breast cancer (BC) and ovarian cancer (OC) are rapidly increasing in Saudi Arabia. BRCA1 and MGMT epimutations have been linked to a higher risk of these malignancies. The present research investigated the impact of these epimutations on the prevalence of BC and OC among Saudi women. DNA methylation was evaluated using methylation-specific PCR, whereas mRNA expression levels were assessed using qRT-PCR. We evaluated white blood cell (WBC)–BRCA1 methylation in 1958 Saudi women (908 BC patients, 223 OC patients, and 827 controls). MGMT methylation was determined in 1534 of the 1958 women (700 BC patients, 223 OC patients, and 611 controls). BRCA1 methylation was detected in 8.6% of the controls and 11% of the BC patients. This epimutation was linked to 13.8% of the early-onset BC patients (p = 0.003) and 20% of the triple-negative breast cancer (TNBC) patients (p = 0.0001). BRCA1 methylation was also detected in 14% of the OC patients (p = 0.011), 19.4% of patients aged <55 years (p = 0.0007), and 23.4% of high-grade serous ovarian cancer (HGSOC) patients. In contrast, the BRCA1 mutation was detected in 24% of the OC patients, 27.4% of patients aged ≥55 years, and 26.7% of the HGSOC patients. However, MGMT methylation was detected in 10% of the controls and 17.4% of the BC patients (p = 0.0003). This epimutation was linked to 26.4% of the late-onset BC patients (p = 0.0001) and 11% of the TNBC patients. MGMT methylation was also found in 15.2% of the OC patients (p = 0.034) and 19.1% of HGSOC patients (p = 0.054). Furthermore, 36% of the BRCA1-methylated patients and 34.5% of the MGMT-methylated patients had a family history of cancer, including breast and ovarian cancer. Notably, BRCA1 and MGMT mRNA levels were greater in the WBC RNA of the BC patients and cancer-free methylation carriers than in that of the OC patients. Our data indicate that BRCA1 and MGMT epimutations significantly contribute to the development of breast cancer and ovarian cancer in Saudi cancer patients. These blood-based biomarkers could help identify female patients at high risk of developing TNBC and HGSOC at an early age.