Breast cancer can never said to be cured since it has been known to recur decades after the initial diagnosis and treatment. While hormone receptor negative (ER-/PR-) breast cancer is more prone to relapse at first, hormone receptor positive (ER+/PR+) disease is more subject to late relapse.
This has prompted some to call for endocrine treatment (aromatase inhibitor or tamoxifen) to continue beyond five years for patients with estrogen responsive disease.
Now a new study has reported that estrogen does not appear to drive the process than lands ER+/PR+ cancer cells in secondary sites where they can remain viable but dormant. However, estrogen fuels the growth of such cells and can help convert micrometastases into tumors.
Hormone responsive breast cancer is most subject to late relapse
Estrogen receptor negative (ER-) breast cancer has been found to be more likely to recur early than ER+ disease. However, the risk of late recurrence is greater for ER+ tumors. One study reported that while the risk of recurrence was lower at first for ER+ compared to ER- disease, ER+ tumor status was more detrimental after 7.7 years.
Given the risk of late recurrence for ER+ disease, some researchers and practitioners are recommending that patients remain on endocrine treatment beyond the five years that has been standard.
Latest research confirms that estrogen fuels metastasis in ER+ breast cancer
The study referenced at the beginning of this news article was designed to investigate drivers of metastasis in an animal model of hormone receptor positive (ER+/PR+) luminal breast cancer. Luminal breast cancer is the most common molecular phenotype, as determined by gene expression profiling, and accounts for half of all breast cancer-specific deaths.
To conduct the study, the authors developed new rodent models of metastatic human luminal breast cancer. It was confirmed that disease progression in the animals mirrored human breast cancer. Primary lesions in the tibia (shinbone) generated locoregional metastases predictably. In addition, systemically injected metastatic (ER+/PR+) MCF-7 cells consistently resulted in metastases in the skeleton, mammary fat pad, and other organs.
The growth of luminal breast cancer metastases was found to be highly dependent on estrogen in these animals. Furthermore, the growth was dose-dependent and withdrawing estrogen quickly halted the growth of metastases. Micrometastases (2 mm or smaller diameter) at secondary sites retained their viability in the absence of estrogen, however they were dormant and did not progress to macrometastases. Apparently, estrogen is not required for homing to and seeding of ER+ cancer cells in secondary sites but is required for the cells to grow into tumors.
The authors conclude that the findings have important implications for the development of targeted anti-metastatic therapy for luminal breast cancer.
Please see our articles on the ER+/PR+ breast cancer prognosis and what ER+/PR+ breast cancer patients and survivors should eat for more information.
Selected breast cancer studies
Eligibility, compliance and persistence of extended adjuvant endocrine therapy for breast cancer
Myrick ME, Schmid SM, Kilic N, Güth U. Eligibility, compliance and persistence of extended adjuvant endocrine therapy for breast cancer. Acta Oncologica. Informa UK Limited; 2011; 51:247-253 10.3109/0284186x.2011.619567
Tamoxifen and Anastrozole As a Sequencing Strategy: A Randomized Controlled Trial in Postmenopausal Patients With Endocrine-Responsive Early Breast Cancer From the Austrian Breast and Colorectal Cancer Study Group
Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, et al. Tamoxifen and Anastrozole As a Sequencing Strategy: A Randomized Controlled Trial in Postmenopausal Patients With Endocrine-Responsive Early Breast Cancer From the Austrian Breast and Colorectal Cancer Study Group. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2012; 30:722-728 10.1200/jco.2011.36.8993
Breast Cancer Recurrence in Older Women Five to Ten Years after Diagnosis
Bosco JL, Lash TL, Prout MN, Buist DS, Geiger AM, Haque R, et al. Breast Cancer Recurrence in Older Women Five to Ten Years after Diagnosis. Cancer Epidemiology Biomarkers & Prevention. American Association for Cancer Research (AACR); 2009; 18:2979-2983 10.1158/1055-9965.epi-09-0607
Time-Varying Effects of Prognostic Factors Associated With Disease-Free Survival in Breast Cancer
Natarajan L, Pu M, Parker BA, Thomson CA, Caan BJ, Flatt SW, et al. Time-Varying Effects of Prognostic Factors Associated With Disease-Free Survival in Breast Cancer. American Journal of Epidemiology. Oxford University Press (OUP); 2009; 169:1463-1470 10.1093/aje/kwp077
Time-varying pattern of recurrence risk for Chinese breast cancer patients
Yin W, Di G, Zhou L, Lu J, Liu G, Wu J, et al. Time-varying pattern of recurrence risk for Chinese breast cancer patients. Breast Cancer Research and Treatment. Springer Science and Business Media LLC; 2008; 114:527-535 10.1007/s10549-008-0022-5