ER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.

The biology and pathomechanism of bilateral breast cancers is not fully understood. We compared the morphological and immunohistochemical characteristics of primary tumors in patients with synchronous bilateral breast cancers and metachronous bilateral breast cancers, with special focus on intrinsic tumor phenotype. Methods: Tumor morphology and expression of 8 immunohistochemical markers were assessed in tissue microarrays containing primary breast tumor cores from 113 metachronous bilateral breast cancers and 61 synchronous bilateral breast cancers. Analyzed markers included hormone receptors (estrogen receptor, progesterone receptor), HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor. Cutoff levels are provided in the table. Results: Metachronous bilateral breast cancers tumors had lower estrogen receptor expression (p=0.047) and higher expression of cytokeratin 5/6 (p=0.017) and of vimentin (p=0.008); in multivariate analysis only vimentin retained the significance (p=0.01). Ten (13%) and 11 (26%) of metachronous bilateral breast cancers and synchronous bilateral breast cancers had luminal A phenotype, 39 (50%) and 15 (36%) were luminal B HER2negative, 13 (17%) and 12 (28%)-luminal B HER2-positive, 3 (4%) and 2 (5%)-HER2-positive (not luminal), and 12 (16%) and 2 (5%) had triple negative phenotype (p=0.07). Conclusion: Metachronous bilateral breast cancers, compared to synchronous bilateral breast cancers, are characterized by more aggressive phenotype, expressed by lower expression of estrogen receptor and stronger expression of cytokeratin 5/6 and vimentin; this does not, however, translate into differences in the distribution of intrinsic tumor phenotypes.

Bones are the most common metastatic site of relapse in breast cancer patients and the prediction of bone metastases (BM) risk might prompt developing preventive and therapeutic strategies. The aim of the study was to correlate imumohistochemical (IHC) expression of selected proteins in primary breast cancer with the occurrence of BM. We analyzed expression of proteins potentially associated with BM in primary tumors of 184 patients with metastatic breast cancer (113 with- and 71 without BM). Expression of estrogen receptor (ER) in primary tumor was more common in patients with- compared to those without BM (74 vs. 45 % respectively, p = 0.0001), whereas in this subset less common was expression of parathyroid hormone related protein receptor type 1 (16 vs. 34 %, respectively, p = 0.007) and cytoplasmic expression of osteopontin (OPNcyt; 1.9 vs. 14 %, respectively, p = 0.002). The relationship between expression of ER and OPNcyt and the occurrence of BM was confirmed in the multivariate analysis. The ER-positive/OPNcyt negative phenotype was significantly more common in patients with- compared to those without BM (75 and 25 %, p < 0.0001, respectively; HR 1.79, p = 0.013). Luminal A (43 vs. 23 % respectively, p = 0.009) and luminal B/HER2-positive (16 vs. 4.9 % respectively, p = 0.032) subtypes were more common in patients with- compared to those without BM, whereas triple negative breast cancer subtype was less common (16 vs. 38 %, p = 0.002).

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Patients with bilateral breast cancer (BBC) and breast-ovarian cancer syndrome (BOCS) constitute populations potentially enriched for molecular defects involved in the pathomechanisms of these malignancies. The aim of our study was to compare tumor morphology and expression of estrogen and progesterone receptor, HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor in tissue microarrays from 199 tumors from BBC or BOCS patients and 199 age-matched solitary tumors. Compared to controls, BBC and BOCS considered jointly had lower incidence of DCIS, lower expression of PgR and HER2, and higher expression of Ki67 and vimentin. BOCS tumors were of higher grade, had lower expression of ER and PgR and higher expression of Ki67, CK5/6, vimentin and EGFR. BBC had less DCIS component, lower HER2 expression and higher Ki67 expression. Metachronous BBC (mBBC) had lower expression of ER, PgR and HER2, and higher expression of Ki67 and vimentin. Synchronous BBC (sBBC) had less DCIS component, higher expression of ER, and lower expression of CK5/6, EGFR and E-cadherin. BBC and breast cancers in BOCS differ in many aspects from solitary tumors. BBC are a heterogeneous group of tumors, differing between sBBC and mBBC. mBBC phenotype shares many features with BOCS tumors.