Risk factors of lung metastases from advanced invasive ductal carcinoma of the breast.

BACKGROUND: The causal mechanisms underlying breast cancer (BC) have yet to be completely elucidated, and the majority of cases of BC appears to occur sporadically in the absence of any known risk factor (RF) or genetic mutation. Metastasis is a crucial event in the progression of the disease and a leading cause of cancer morbidity and mortality. Because BC is a heterogeneous disease, RFs affecting the onset of metastases remain unclear, and more needs to be learned about mechanisms that control this process. The aim of this study was to evaluate the weight of RFs such as age<50 years, estrogen receptor (ER) negativity, human epidermal growth factor 2 (HER2) positivity, high histological nuclear grading (G2-3), and preoperative carbohydrate tumor-related antigen serum levels >50 U/mL (CA 15-3>50), in a small group of patients with advanced BC who underwent curative surgery and adjuvant postoperative therapy, and developed lung metastases (LMs). PATIENTS & METHODS: Eight women (median age 61, range 45-73 years) with stage II-III BC (cases) and no evidence of distant metastasis (M0) at the time of diagnosis underwent curative surgery (lumpectomy or mastectomy plus sentinel lymph node biopsy or axillary node dissection) followed by adjuvant chemotherapy, and/or endocrine therapy (selective estrogen receptor modulators or aromatase inhibitors) or targeted immunotherapy (trastuzumab). All patients developed LMs during follow-up. Controls were 15 age- and stage-matched M0 women with BC. 18F-FDG-PET/CT was used for staging all patients. Odds ratio (OR) estimates and the associated 95% confidence interval (CI) were calculated. The significance level, using Fisher exact test, was set at p<0.05. RESULTS: Age<50 years (OR=1.09, 95%CI 0.15-7.8, p=0.66) and ER negativity (OR=1.65, 95%CI 0.26-10.31, p=0.46) were statistically nonsignificant RFs, while the presence of bone metastasis (OR=2.75, 95%CI 0.45-16.50, p=0.25), CA15-3>50 U/mL (OR=3.33, 95%CI 0.55-19.94, p=0.18), and G2-3 (OR=4.00, 95%CI 0.61-26.12, p=0.15) were weak RFs. HER2 positivity was the only statistically significant (OR=10.83, 95%CI 1.37-85.44, p=0.02) RF of LMs from BC. In conclusion, patients with stage II-III HER2+ BC have a significantly (p<0.05) increased (>10-fold) risk of developing LMs during follow-up.