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.

Risk of breast cancer recurrence remains for many years

Risk of breast cancer relapse persists for many years. One study found that the risk of recurrence between years five to 12 averages approximately 4% per year. Other studies have found that the rate of recurrence for early-stage breast cancer after the 10-year mark is 1% to 2% overall. While rare, recurrences as long as 35 years after the initial breast cancer diagnosis have been reported. While relapse during the first five years is associated with factors such as large number of positive lymph nodes, poorly differentiated tumor, or lumpectomy without radiotherapy, the few studies that have examined very late recurrence (10 years or longer after initial breast cancer diagnosis) have not found that similar factors are linked to it. Hormone receptor status appears to be the only attribute consistently associated with very late recurrence.

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 latest research concerning hormone receptor positive breast cancer prognosis and what ER+/PR+ breast cancer patients and survivors should eat for more information.