The lymph node ratio as an independent prognostic factor for non-metastatic node-positive breast cancer recurrence and mortality.

PURPOSE: To examine the prognostic value of lymph node ratio (LNR) in pathological nodal (pN) stage breast cancer patients. Also, to analyse additional clinical and pathologic prognostic factors and the impact of LNR among molecular subtypes. METHODS: Among a total of 3088 patients, 1004 women with non-metastatic lymph node-positive breast cancer were analysed. The patients were classified into low (≤0.20), intermediate (0.20 to 0.65) and high-risk (>0.65) LNR groups. Univariate and multivariate Cox proportional hazards regression model for disease-free survival (DFS), and overall survival (OS) were performed to evaluate the prognostic value of LNR. RESULTS: The median LNR was 0.17 (range 0.02-1.00). Of the patients, 55.7% were in low, 32.1% in intermediate, and 12.3% in high risk group. When compared with low risk group, high risk group had more often large tumor size and high grade tumor with lymphovascular invasion. The median follow-up period was 46.8 months. The 5-year breast cancer-specific OS and DFS rates for patients with low, intermediate, and high were 88%-67%, 65%-48% and 53%-24%, respectively (both plog-rank<0.0001). On multivariate analysis, pN stage and LNR were both independent predictors of survival, however, an overlapping between N1 (250 months, 95% confidence interval [CI] 88.15-413.21) and N2 (176 months, 95% CI 129.51-222.93) curves in pN staging was determined. We also observed clear prognostic separation for triple negative breast cancer with LNR survival over pN staging. CONCLUSION: The LNR predicts survival more accurately than pN staging in node-positive breast cancer patients. The use of LNR may standardize the staging and guide decisions for adjuvant treatments.

Association between common risk factors and molecular subtypes in breast cancer patients.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer. METHODS: This cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis. RESULTS: Thousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15-1.74; p=0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01-2.25; p=0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03-2.13; p=0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83-1.88; p=0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47-0.97; p=0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53-1.04; p=0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93-5.17; p=0.04) and luminal A (OR 1.87, 95% CI 0.93-3.90, p=0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06-3.37; p=0.04 and OR 1.90 95% CI 1.00-3.61; p=0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43-0.95; p=0.02 and OR 0.50 95% CI 0.32-0.76; p=0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands. CONCLUSIONS: Reproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.

Metaplastic breast carcinoma: case series and review of the literature.

Metaplastic breast carcinoma (MpBC) is a rare disease entity, accounting for less than 1% of all breast carcinomas. Furthermore, it is a heterogenous disease with different subgroups, including malignant epithelial (carcinoma) and stromal (sarcoma) features. Here we evaluated, retrospectively, 14 female MpBC patients admitted to Ankara Oncology Training and Research Hospital between 2005 and 2011. Median age was 45.5 (range:16.0-76.0) and tumor size 57.5 mm (range: 20.0-80.0 mm). Histopathological subtypes were as follows: 5 carcinosarcoma, 5 squamous and 4 adenosquamous carcinoma. All but one with upfront lung metastasis, had their primary breast tumor operated. Axillary lymph nodes were involved in 64.3%. The most common sites of metastasis were lungs and brain. Chemotherapy including antracycline, taxane and even platinium was planned for adjuvant, neoadjuvant and palliative purposes in 9, 3 and 1 patient, respectively. Median cycles of chemotherapy was 6 (range:4-8). Median follow-up of the patients was 52 months (95%CI 10.4-93.6 month). Median 3 year progression free survival (PFS) and overall survival (OS) in this patients cohort were 33% and 56%, respectively. In conclusion, MpBC is a rare and orphan disease without standardized treatment approaches and the prognosis is poor so that larger studies to investigate different treatment schedules are urgently needed.