E73 Hormone-dependent tissues - Breast

Topic

The defining characteristic of this group of tumors is that their net proliferation rate—the balance between dividing and dying tumor cells—is directly modulated by the concentration of a specific hormone: in estrogen-receptor-positive breast cancer, this hormone is estrogen itself, while in prostate cancer, it is testosterone and its more active derivative, dihydrotestosterone.

A simulator for this type of tumor can replicate the events following hormonal suppression via treatment—a process known as the "castration response": when the hormone is suppressed, the tumor's net proliferation rate falls below its rate of programmed cell death; consequently, the tumor stops growing and begins to shrink.

However, this tumor regression is not permanent; over time, a clone of tumor cells may emerge that no longer relies on the hormone to divide—a castration-resistant clone that resumes tumor growth even in the absence of the hormone previously required.

In addition to this hormonal mechanism, each of these two tumors exhibits a characteristic and particularly significant metastatic pattern: prostate cancer tends to spread preferentially to the bone, whereas breast cancer tends to spread preferentially to the axillary lymph nodes.

Prostate cancer spreads preferentially to the bone because bone marrow cells release a signaling molecule that specifically attracts prostate cancer cells—which, in turn, possess the corresponding receptor on their surface. The prostate tumor cell follows the gradient of this signaling molecule—which becomes increasingly concentrated as the cell approaches the bone marrow—until it reaches and colonizes the tissue. Breast cancer, in contrast, spreads preferentially to the axillary sentinel lymph node—that is, the first lymph node into which the tumor drains—because the tumor itself releases a chemical substance that stimulates the growth of new lymphatic vessels in that direction, thereby opening a direct path from the tumor to that sentinel lymph node.

It is this dual dependency—on a hormone for growth and on a specific chemical gradient for spread—that explains why these hormone-dependent tumors can initially be treated by suppressing the relevant hormone, and why, when a castration-resistant clone eventually emerges, the tumor regains its ability to grow and spread via its characteristic metastatic route: whether to the bone in the case of prostate cancer, or to the axillary sentinel lymph node in the case of breast cancer.

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