BREAST CANCER
TYPES
There are different types of breast cancer depending on the location and origin of the cancer, its biochemical composition (such as seen in histology slides), its genetic makeup (such as seen in microarray analysis) and, most importantly, its responsiveness or irresponsiveness to different messenger molecules, especially hormones and proteins. In particular, such molecules include the female reproductive hormones estrogen and progesterone, as well as the protein HER2. Based on these criteria, four main types of breast cancers can be distinguished. Luminal A breast cancer cells, which seem to be the most common type of breast cancer, possess both estrogen and progesterone receptors, but do not produce HER2 (or produce very low levels of it). Depending on individual studies, it is estimated that the Luminal A type makes up for about 37-73% of all breast cancers. Luminal B breast cancer cells are responsive to the hormone estrogen, but often show only weak or no response to the hormone progesterone. According to different studies, the Luminal B type makes up for about 8-11% of all breast cancers. HER2-positive breast cancer cells are characterized by their ability to produce the HER2 protein, a molecule that is created from the HER2 oncogene and facilitates growth of the cancer cells. In addition to being able to produce the HER2 protein, HER2 cancer cells may or may not also have receptors for either of both of the hormones estrogen and progesterone. About 5-11% of all breast cancers are estimated to be HER2-positive cancers. Lastly, there are Basal-type (triple negative) breast cancer cells. As the name indicates, these cancer cells do not produce HER2, nor are they receptive to either estrogen or progesterone hormones. About 11-26% of all breast cancers are estimated to be the Basal-type (triple negative). Differentiation between different subtypes is important, because the biochemical and genetic makeup of each subtype offers specific treatment options and approaches.
Luminal A
Luminal A breast cancer is a slow-growing, non-metastasizing type of cancer usually originating from ductal cells of the breast. The cellular makeup of this type of cancer is very similar to that of the original (normal) cells of the duct (well-differentiated) . It displays receptors for both estrogen and progesterone hormones on its surface, but does not overproduce HER2 protein. It is not only the most common type of breast cancer (between about 37-73% of all breast cancers are Luminal A), but also presumably the type of breast cancer that can be most successfully treated and has high survival rates. Although Luminal A type breast cancer has traditionally been treated with chemotherapy, recent research seems to suggest that hormone therapy is very effective for this type of breast cancer. This is because, due to their hormone receptors for both estrogen and progesterone, the metabolism and replication of Luminal A type cancer cells can be down regulated by adjusting the availability of these hormones. While hormone therapy comes with its own set of side effects, many of which comparable to the onset of menopause due to the decreased availability of reproductive hormones, many women experience such side effects as less disruptive than those of chemotherapy. Therefore, hormone therapy not only provides promising targeted (personalized) treatment options for the future, but also gives hope that chemotherapy may not necessarily be required for this type of cancer as research and development progress. In fact, even now, Luminal A breast cancer is often successfully treated with localized surgery (lumpectomy) and radiation therapy, if it is detected early enough and still small in size.
Luminal B
Luminal B breast cancers are faster growing than their Luminal A counterpart, but not as fast as the more aggressive HER2-positive and Basal-type (triple negative) breast cancers. Luminal B cancer cells can originate from either ductal or lobular structures. They can also develop from Luminal A cells that proliferate and slowly turn more aggressive as they grow into larger masses. Because Luminal B cancer cells are more aggressive, they also tend to infiltrate surrounding breast tissues more and metastasize to remote locations through the blood or lymphatic system. Treatment for this type of cancer is complex. Due to the estrogen (but not progesterone) receptor on their surface, these cells may respond to hormone therapy. However, because of their more aggressive and multi-focal nature, a mastectomy (removal of the whole breast), as well as chemo and radiation therapy may also often be necessary for Luminal B cancers.
HER2-positive
HER2-positive cancer is a fast-growing, metastasizing (spreading to other regions of the body, such as the nervous system), and aggressive type of cancer. It is comparably rare (up to 20% of all breast cancers, though percentages vary in the literature, and some large population-based studies estimate its prevalence at only about 10% of all breast cancers). HER2 is a growth protein that is over expressed in these cancer cells, thus causing them to grow more rapidly than functional breast cells, and form tumors. Although HER2-positive cancer can be both hormone receptor positive or negative for either estrogen or progesterone, the presence of excess HER2 protein seems to inhibit hormone therapy efficiency, thus making treatment of HER2-positive cancer challenging. For instance, it seems that HER2 over-expression is often cross-linked to reduced reactivity of the cancer cells to endocrine (hormone) therapy. HER2 protein, which like hormone receptors is expressed on the cellular surface, can lead to hormone therapy resistance and effectively interfere with the pathways of hormone therapy, although the mechanisms of this are not conclusively understood. Traditional treatment is of HER2-positive breast cancers is surgery (lumpectomy or mastectomy depending on the size of the tumor) and chemotherapy based, although modern approaches have developed a combined treatment of these methods with targeted HER2 antagonists (medications, such as antibodies, that suppress the expression of HER2 protein on the cellular surface). Recent research even suggests that such antagonists can be able to restore sensitivity to endocrine therapy, and might offer chemotherapy-free treatment options in the future, at least for early-stage HER2-positive cancers.
Basal-type (triple negative)
Basal-type (triple negative) breast cancers are a highly aggressive molecular subtype of cancer which grow fast and invasively, infiltrating surrounding healthy breast tissues. They have a high rate of recurrence and often affect young women. They are called triple negative, because they typically lack both steroid hormone receptors (estrogen and progesterone) and HER2 protein markers on their cell surface. This also makes them especially elusive for personalized therapies, which need to be able to target some particular type of molecular marker. Because targeted treatments are not presently developed for this type of breast cancer, chemotherapy (combined with either lumpectomy or mastectomy) remains the only treatment option for patients with basal-type (triple negative) cancer. However, because these cancers are fast replicating, they are usually responsive to chemotherapy, which tends to be rather effective for basal-type (triple negative) breast cancers. Moreover, biomolecular markers which could serve as specific targets for personalized treatments are currently being studied, and there is hope that such treatment will be developed in the not too distant future.