Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis.

Prior studies have suggested that the type of breast cancer influences the location of distant metastases ("organotropism") and that there may be discordance of estrogen receptor and human epidermal growth factor receptor 2 (Her2) expression between primaries and metastases. Our aims were to investigate the relationship between tumor type and metastatic site and to compare biomarker expression between primary and metastatic tumors. We retrospectively reviewed 102 biopsy-proven cases of breast cancer metastatic to distant sites from 2000 to 2010 and 34 corresponding primaries for histologic subtype, grade, lymphovascular invasion, lymph node metastasis, and expression of estrogen receptor and Her2. Most metastases were of ductal (88) and lobular (11) histologic types. Available data on primaries indicated that the majority were grade III with positive lymph node metastasis and lymphovascular invasion. Biomarkers on 73 metastases showed 37 estrogen receptor positive/Her2-, 6 estrogen receptor positive/Her2+, 8 estrogen receptor negative/Her2+, and 22 estrogen receptor negative/Her2-. The most common metastatic sites were the lung (26%), bone (32%), and liver (21%). We found no association between estrogen receptor/Her2 profile and metastatic site (P = .16). When compared with ductal carcinoma, lobular carcinoma showed a unique metastatic pattern to gastrointestinal tract/gynecologic sites (P = .014). Of 34 cases with paired prognostic markers for primary and metastatic sites, 7 (20%) demonstrated discordance in estrogen receptor-positive/Her2 profile between the primary and the metastasis. Because the estrogen receptor-positive/Her2 profile of metastatic breast cancer did not always match that of the primary tumor, it is important to repeat the prognostic markers of metastasis.

St Romain P ，Madan R ，Tawfik OW ，Damjanov I ，Fan F ... -  《-》

Discordant expression of hormone receptors and HER2 in breast cancer. A retrospective comparison of primary tumors with paired metachronous recurrences or metastases.

Arapantoni-Dadioti P ，Valavanis C ，Gavressea T ，Tzaida O ，Trihia H ，Lekka I ... -  《Journal of BUON》

Bone metastasis is strongly associated with estrogen receptor-positive/progesterone receptor-negative breast carcinomas.

Wei B ，Wang J ，Bourne P ，Yang Q ，Hicks D ，Bu H ，Tang P ... -  《-》

Primary and secondary distant metastatic breast cancer: two sides of the same coin.

This study evaluated the differences between breast cancer (BC) patients who present with primary distant metastatic disease (PMD) and those who develop distant metastases during the course of their illness (secondary metastatic disease [SMD]) with regard to clinicopathological characteristics, patterns of metastatic sites, palliative therapy and survival. Based on a cohort of patients with newly diagnosed BC (n = 1459), we analyzed all patients who had PMD (n = 92, 6.3%) and those who developed SMD (n = 277, 20.3%). There were no significant differences with regard to the patient's age in which metastatic disease had been diagnosed (PMD/SMD: 64 years/66 years, p = 0.19). The SMD group had more often triple-negative carcinomas (25.5%/7.3%, p = 0.019); there were no significant differences with regard to grading (p = 0.61), HER2 status (p = 0.67) and hormonal receptor status (p = 1.00). The mean number of metastatic locations was similar (2.3/2.3, p = 0.91). While patients with PMD usually initiated systemic therapy, patients with SMD received systemic therapy after diagnosis of metastatic disease less often (16.4%/2.6%, p < 0.001). Both groups received palliative chemotherapy similarly often (PMD/SMD: 62.8%/63.3%, p = 1.00). The mean number of palliative therapy lines was similar (PMD/SMD: 2.8/3.2, p = 0.39). Compared to patients with SMD, patients who had PMD had a significantly improved metastatic disease survival (p < 0.001). The one-year, two-year and five-year survival rates were as follows: 76.9%/60.3%, 58.2%/43.0%, 23.1%/10.6%. The median survival times were 18.5 months and 32 months. The poorer prognosis of patients with SMD may be explained by differences in clinicopathological features of the tumor, metastatic patterns, the use palliative therapy and drug resistance of the tumor cells which occurs in therapy-naïve PMD patients at a later phase of the disease course.

Güth U ，Magaton I ，Huang DJ ，Fisher R ，Schötzau A ，Vetter M ... -  《-》

HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process.

The objective of this study was to determine whether HER2 expression levels in breast carcinomas were modified by chemotherapy or during the metastatic process. HER2 expression was analyzed on sequential tissue specimens taken from the primary tumor before patients received preoperative chemotherapy (CT) and from post-CT residual breast tumor or at a metastatic site. The first group of patients included 59 women who presented with T2-T4,N1-N2 breast carcinoma and were treated by preoperative anthracycline-based CT and then underwent surgery. The second group included 44 patients with metastatic breast carcinoma localized to the lung (27 patients) or to the liver (17 patients). HER2 status was determined by immunohistochemistry using an anti-p185(HER/neu) monoclonal antibody and was classified as overexpressed or not overexpressed. Among the patients who received preoperative CT, HER2 overexpression was observed in 15 of 59 patients (25%). A complete pathologic response was observed in 2 of these 15 patients. HER2 still was overexpressed in 11 of 13 remaining residual tumors and was no longer detectable in 2 tumors. In addition, the 29 tumors with no HER2 overexpression before CT remained negative after treatment. In patients with metastatic breast carcinoma, HER2 was overexpressed in 11 of 44 primary tumors (25%). In 9 of these 11 tumors, HER2 overexpression was maintained in the metastases (9 pulmonary metastases and 4 hepatic metastases). In two patients who had low levels of HER2 overexpression in their primary tumors, no staining was observed in the secondary tumor (one pulmonary tumor and one liver tumor). There were no tumors in which the overexpression of HER2 was found only in the metastasis. The current study showed that, in most patients, HER2 overexpression was unchanged after CT and in metastatic sites. No HER2 negative primary tumors became HER2 positive after patients received CT or during the metastatic process. In a few patients, a diminution in the level of HER2 expression was observed after CT or in secondary tumors. This may have been due to a transitory state of altered tumor cells or to the selection of HER2 negative tumor cells clones.

Vincent-Salomon A ，Jouve M ，Genin P ，Fréneaux P ，Sigal-Zafrani B ，Caly M ，Beuzeboc P ，Pouillart P ，Sastre-Garau X ... -  《CANCER》