Estrogen and progesterone receptors (ER/PR) were measured in primary tumors and metastases of 397 breast cancer patients. Survival following mastectomy was significantly longer in patients with ER and PR positive tumors, as was survival after first recurrence. The prognostic value of ER and PR was compared with such clinical factors as disease‐free interval (DFI) and the dominant site of first metastasis by Cox's regression analysis. With all the different therapy modalities long DFI was the best prognostic indicator. However, in the patient group treated with endocrine therapy, ER and PR positivity was the best prognostic indicator, suggesting that longer survival in receptor positive patients was related to the response to endocrine treatment. Cancer 56: 1696‐1700, 1985.

Significance of estrogen and progesteron receptor, disease-free interval, and site of first metastasis on survival of breast cancer patients

Nearly all fatalities arising from breast tumors are attributable to distant metastases. Breast cancer liver metastasis (BCLM) is associated with poor prognoses, with the median survival time being 2 to 3 years. Tumor intrinsic subtype directs preferential metastasis to specific organs, with HER2-enriched tumors demonstrating the highest rates of metastasis to the liver, though all subtypes can grow in the liver. There is no singular established standard-of-care for BCLM; therapeutic selection is driven by histologic and molecular hallmarks of the primary tumor or biopsied metastasis samples. Given the poor prognosis of patients with hepatic spread, pre-clinical studies are necessary to identify and evaluate promising new treatment strategies. It is critical that these laboratory studies accurately recapitulate the BCLM disease process, standard progression, and histological attributes. In this review, we summarize the histologic and molecular characteristics of BCLM, evaluate the efficacy of existing surgical and medical treatment strategies, and discuss future approaches to preclinical study of BCLM.

Breast cancer liver metastasis: current and future treatment approaches

Progress in cancer therapies has resulted in improved survival of patients with early stage breast cancer. However, mortality remains high in patients with distant recurrence of the disease after initially successful treatment of early stage breast cancer. To this end, tumor recurrences have been attributed to the presence of dormant tumor cells in breast cancer patients and cancer survivors. Current clinical practice guidelines recommend a "wait-and-watch" approach for tumor recurrence. This is because of our limited understanding of tumor dormancy. Dormant tumor cells are quiescent, and thus, do not respond to chemotherapies or radiation therapies, and they are not operable. Therefore, immunotherapy is the only option for the treatment of tumor dormancy. However, gaps in our knowledge as to dormancy-specific antigens prevent a relapse preventing vaccine design. Here, I provide a critical review of cancer immunotherapy, and discuss empirical evidence related to naturally occurring tumor dormancy and treatment-induced tumor dormancy at the site of primary tumor and in distant organs before and after cancer therapies. Finally, I suggest that personalized vaccines targeting dormancy-associated neoantigens, which can be given to patients with early stage disease after the completion of neoadjuvant therapies and tumor resection as well as to cancer survivors could eliminate relapse causing dormant cells and offer a cure for cancer.

The premise of personalized immunotherapy for cancer dormancy

Background: Population-based estimates for prognosis among patients with liver metastases in newly diagnosed breast cancer are not generally available. Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, we identified 298,370 patients with breast cancer and 4,285 patients diagnosed with initial liver metastases between 2010 and 2014. Data were stratified according to subtype, age, and race. Multivariate logistic and Cox regression were used to identify predictors for the presence of initial liver metastases and prognostic factors, respectively. Kaplan–Meier procedure was used for survival analysis. Results: A total of 4,285 patients with initial liver metastases (1.4% of the entire cohort, 29.6% of the subset with metastatic disease) were identified. Patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (4.4% of entire cohort, 52.5% of patients with metastatic disease to any distant site) and HR-positive HER2-positive (2.8% of entire cohort, 40.4% of patients with metastatic disease to any distant site) subtypes had highest incidence proportions. The median survival of patients with liver metastases in the entire cohort was 15.0 months. Patients with HR-positive HER2-positive subtype showed the longest median survival (31.0 months); however, patients with triple-negative subtype showed the shortest median survival (8.0 months). Conclusions: Our findings provide population-based estimates of epidemiologic characteristics and prognosis in breast cancer patients diagnosed with initial liver metastases. Impact: This study lends support to the diagnosis of the liver among patients at high risk of liver metastases, including those with HER2-positive and other systemic metastases.

/pdf/a-population-based-study-on-liver-metastases-in-women-with-4kpi1eyl7n.pdf

A Population-Based Study on Liver Metastases in Women with Newly Diagnosed Breast Cancer.

FN14 has been implicated in many intracellular signaling pathways, and GRP94 is a well-known endoplasmic reticulum protein regulated by glucose. Recently, both have been associated with metastasis progression in breast cancer patients. We studied the usefulness of FN14 and GRP94 expression to stratify breast cancer patients according their risk of brain metastasis (BrM) progression. We analyzed FN14 and GRP94 by immunohistochemistry in a retrospective multicenter study using tissue microarrays from 208 patients with breast carcinomas, of whom 52 had developed BrM. Clinical and pathological characteristics and biomarkers expression in Luminal and non-Luminal patients were analyzed using a multivariate logistic regression model adjusted for covariates, and brain metastasis-free survival (BrMFS) was estimated using the Kaplan-Meier method and the Cox proportional hazards model. FN14 expression was associated with BrM progression mainly in Luminal breast cancer patients with a sensitivity (53.85%) and specificity (89.60%) similar to Her2 expression (46.15 and 89.84%, respectively). Moreover, the likelihood to develop BrM in FN14-positive Luminal carcinomas increased 36.70-fold (3.65-368.25, p = 0.002). Furthermore, the worst prognostic factor for BrMFS in patients with Luminal carcinomas was FN14 overexpression (HR = 8.25; 95% CI: 2.77-24.61; p = 0.00015). In these patients, GRP94 overexpression also increased the risk of BrM (HR = 3.58; 95% CI: 0.98-13.11; p = 0.054-Wald test). Therefore, FN14 expression in Luminal breast carcinomas is a predictive/prognostic biomarker of BrM, which combined with GRP94 predicts BrM progression in non-Luminal tumors 4.04-fold (1.19-8.22, p = 0.025), suggesting that both biomarkers are useful to stratify BrM risk at early diagnosis. We propose a new follow-up protocol for the early prevention of clinical BrM of breast cancer patients with BrM risk.

/pdf/predictive-and-prognostic-brain-metastases-assessment-in-2sa4f0t9zj.pdf

Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients: FN14 and GRP94 from Diagnosis to Prophylaxis.

Purpose: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergon

/pdf/biological-subtypes-and-distant-relapse-pattern-in-breast-1scnbcrvvz.pdf

Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology).

e11559 Background: Relapse is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of th...

Biologic subtypes and first relapse pattern in curative surgery performed breast cancer patients: Study of Anatolian Society of Medical Oncology.

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Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology).

Biologic subtypes and first relapse pattern in curative surgery performed breast cancer patients: Study of Anatolian Society of Medical Oncology.