Predictive value of DNA repair gene expression for response to neoadjuvant chemotherapy in breast cancer.

Genome-wide analysis using microarrays has revolutionized breast cancer (BC) research. A substantial body of evidence supports the clinical utility of the 21-gene assay (Oncotype DX) and 70-gene assay (MammaPrint) to predict BC recurrence and the magnitude of benefit from chemotherapy. However, there is currently no genetic tool able to predict chemosensitivity and chemoresistance to neoadjuvant chemotherapy (NACT) during BC treatment. In this study, we explored the predictive value of DNA repair gene expression in the neoadjuvant setting. We selected 98 patients with BC treated with NACT. We assessed DNA repair expression in 98 formalin-fixed, paraffin-embedded core biopsy fragments used at diagnosis and in 32 formalin-fixed, paraffin-embedded post-NACT residual tumors using quantitative reverse transcription-polymerase chain reaction. The following genes were selected: BRCA1, PALB2, RAD51C, BRCA2, ATM, FANCA, MSH2, XPA, ERCC1, PARP1, and SNM1. Of 98 patients, 33 (33.7%) achieved pathologic complete response (pCR). The DNA expression of 2 genes assessed in pre-NACT biopsies (PALB2 and ERCC1) was lower in pCR than in non-pCR patients (P=0.005 and P=0.009, respectively). There was no correlation between molecular subtype and expression of DNA repair genes. The genes BRCA2 (P=0.009), ATM (P=0.004), FANCA (P=0.001), and PARP1 (P=0.011) showed a lower expression in post-NACT residual tumor samples (n=32) than in pre-NACT biopsy samples (n=98). The expression of 2 genes (PALB2 and ERCC1) was lower in pCR patients. These alterations in DNA repair could be considered suitable targets for cancer therapy.

Predictive value of DNA repair gene expression for response to neoadjuvant chemotherapy in breast cancer

Genome-wide analysis using microarrays has revolutionized breast cancer (BC) research. A substantial body of evidence supports the clinical utility of the 21-gene assay (Oncotype DX) and 70-gene assay (MammaPrint) to predict BC recurrence and the magnitude of benefit from chemotherapy. However, there is currently no genetic tool able to predict chemosensitivity and chemoresistance to neoadjuvant chemotherapy (NACT) during BC treatment. In this study, we explored the predictive value of DNA repair gene expression in the neoadjuvant setting. We selected 98 patients with BC treated with NACT. We assessed DNA repair expression in 98 formalin-fixed, paraffin-embedded core biopsy fragments used at diagnosis and in 32 formalin-fixed, paraffin-embedded post-NACT residual tumors using quantitative reverse transcription-polymerase chain reaction. The following genes were selected: BRCA1, PALB2, RAD51C, BRCA2, ATM, FANCA, MSH2, XPA, ERCC1, PARP1, and SNM1. Of 98 patients, 33 (33.7%) achieved pathologic complete response (pCR). The DNA expression of 2 genes assessed in pre-NACT biopsies (PALB2 and ERCC1) was lower in pCR than in non-pCR patients (P=0.005 and P=0.009, respectively). There was no correlation between molecular subtype and expression of DNA repair genes. The genes BRCA2 (P=0.009), ATM (P=0.004), FANCA (P=0.001), and PARP1 (P=0.011) showed a lower expression in post-NACT residual tumor samples (n=32) than in pre-NACT biopsy samples (n=98). The expression of 2 genes (PALB2 and ERCC1) was lower in pCR patients. These alterations in DNA repair could be considered suitable targets for cancer therapy.

Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction.

BACKGROUND: A small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features. METHODS: We studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥ 14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied. RESULTS: Median follow up time was 74 months (range 3-165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥ 25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR. CONCLUSION: Luminal B/HER2 positive, triple negative subtypes and BMI ≥ 25 are independent prognostic factors for risk of LRR after IBR.