Typical medullary breast carcinoma: Clinical outcomes and treatment results

To the Editor: According to the WHO classification, medullary carcinoma is a wellcircumscribed tumor (with pushing margins), composed of poorly differentiated cells with scant stroma and prominent lymphoplasmocytic infiltration. The cells of classic medullary carcinoma are characterized by abundant cytoplasm and pleomorphic high-grade vesicular nuclei. They are arranged in syncytial structures which constitute at least 75% of histologically sampled areas. What is more, the histologic texture of medullary carcinoma lacks tubular differentiation. The abovementioned criteria are similar to those presented by Ridolfi et al. in 1997. Tumors displaying all these definitive characteristics are classified as classic or typical medullary carcinomas. According to WHO, typical medullary breast carcinoma (T-MBC) accounts for less than 1% of all malignant breast neoplasms. Immunohistochemically T-MBC is usually characterized by features typical of basal-like carcinomas; it does not express estrogen (ER), progesterone (PgR), and HER2/neu receptors. Hence, it is included in so-called “triple-negative” breast carcinomas. We would like to present the clinical characteristics and treatment results for 120 patients with T-MBC treated (between 1970 and 2005) at a single institution in Poland (Maria SklodowskaCurie Memorial Cancer Center and Institute of Oncology in Krakow). These cases represent 1.1% of all (11 270) patients treated for breast cancer during this period in our Center. The clinopathologic characteristic of our patients with T-MBC was as following: (i) mean age was 51 years (range: 26-72), (ii) the clinical stage (according to TNM UICC): Ist in 26 patients (21.6%), IInd in 80 (66.7%), and IIIrd in 14 (11.7%), (iii) the diameter of breast tumor (pT) was less than 5 cm in 115 patients (95.8%), (iv) metastases in the axillary lymph nodes occurred in just 10 patients (8.3%), (v) immunonegativity of ER and PgR was observed respectively in 112 patients (93.3%) and in 115 patients (95.8%), (vi) and absence of HER2/neu receptor expression in 105 patients (87.5%). All the patients underwent primary surgery. Radical mastectomies (Halsted during the period 1970-1982, Patey or Madden in 19832005) were performed in 98 (81.6%) patients, while the other 22 (18.4%) patients treated between 1995 and 2005 underwent breastconserving surgery (BCS). The adjuvant radiotherapy (with dose of 50 Gy given in 25 fractions) was performed in 36 patients (30.0%); in all who underwent BCS, and in 14 (with pN+, and/or pT>5 cm) followed mastectomy. Patients with nodal involvement received adjuvant chemotherapy according to a cyclophosphamide, methotrexate, and 5-fluorouracil schedule. Endocrine therapy with tamoxifen was administered to eight (6.7%) patients with PgR and/ or ER expression. The 10-year disease-free survival rate was 90%, and it was not confirmed whether any of the analyzed factors (population, clinical, microscopic, immunohistochemical) had a statistically significant influence on survival rate. During follow-up, only four patients (3.3%) developed distant metastases which were located in bones, lungs, brain, or liver and this failure was case of death in them. To sum up, above we presented the clinical characteristics and treatment results for patients with T-MBC at the same institution and we discussed the controversial problems relating to adjuvant systemic treatment of this rare breast cancer. Our observations of clinicopathologic characteristics of T-MBC patients are similar as presented in the literature. However, it is important to stress that making strict comparisons between the present study group of patients and groups presented by other authors is very difficult and is a questionable approach, since a T-MBC diagnosis itself is problematic and controversial. In an analysis of 13 controlled clinical studies, Huober et al. observed negative estrogen and progesterone receptors in 81% of patients. According to data from the literature, the 10-year survival rate for patients with MBC varies between 63% and 94.9% (our results were 90%). These span mainly result from differences in the clinical and microscopic composition (T-MBC versus invasive carcinoma NST with medullary features) of the groups of patients being compared. The vast majority of the researchers stress that the prognosis for patients with MBC is good or even very good, especially in the case of T-MBC, and is significantly better than among patients with invasive ductal carcinoma. Undoubtedly surprising is the fact that the prognosis for T-MBC, i.e., “triple-negative breast cancer,” is, despite its morphologically malignant features, good or even very good, indeed significantly better than it is for infiltrate ductal breast carcinoma. Most authors reckon that this is due to the presence of the abundant lymphoplasmacytic infiltration that is inseparably associated with this cancer.