Editor’s Note: This week, Rita Wilson disclosed to People Magazine in an exclusive statement that she has been recently diagnosed with breast cancer and has undergone bilateral mastectomy and reconstructive surgery. Below, Dr. V.K. Gadi provides a detailed discussion of Wilson’s underlying condition— LCIS (lobular carcinoma in situ) — and what treatment options should be considered for women with this condition. Gadi is a medical oncologist who specializes in caring for women with breast cancer at Seattle Cancer Care Alliance. He is also a researcher at Fred Hutchinson Cancer Research Center.
What is LCIS and how is it related to invasive lobular carcinoma?
Ms. Wilson has a cancer that has arisen from cells that line the breast lobules, the structures that produce milk following a pregnancy. Most commonly, her lobule cells have accumulated mutations over many years that have resulted in an inappropriate program to divide more rapidly than normal.
The initial result of this growth is to "clog" the lobules — a finding described as lobular carcinoma in situ (LCIS). This is a common finding and considered generally a "non-obligate precursor" for (i.e., could become but usually does not become) invasive cancer.
Over time additional mutations arise, allowing the cells to break through the lobule lining and invade the surrounding normal breast tissue, hence the term invasive or infiltrating lobular carcinoma. The importance of this is three-fold.
- Invasive cancers cause architectural distortion of the normal tissues. What is actually seen on scans such as mammography or ultrasound is this change in the normal tissues.
- Second, invasive cancers cause swelling (edema) as they destroy normal tissue, thus resulting in an actual "mass" that sometimes can be felt by a patient.
- Third, by virtue of no longer being constrained to the inside of the lobule, invasive cancers can now travel to local places such as the lymph nodes under the arm but potentially to any part of the body including but not limited to the bone, lung, liver, or brain.
It is noteworthy that lobular carcinomas are missing (mutated) for one gene in particular called e-cadherin. When this gene is functionally missing, cancer cells can grow unattached to each other and march along "single-file" in the breast tissue. Because of this slightly different growth pattern than other breast cancers, lobular cancer can grow to very large sizes and often metastasize to the lymph nodes before being clinically detected by mammography or other techniques.
Under the microscope, LCIS that has become invasive lobular cancer can be hard to discern. Obtaining a second opinion on pathology can help clarify difficult cases such as Wilson’s.
One additional point about Wilson’s cancer is that she describes a recent change to increased "pleomorphism." This term simply means that under the microscope, the LCIS had recently taken on some concerning changes and was starting to look like other more disorganized cancers. The risk of being associated with invasive cancer goes up when pleomorphism sets in. Most lobular invasive cancers retain very favorable biologic characteristics such as being positive for hormone receptors, having a low tumor grade under the microscope, and a low dividing rate if measured.
How is LCIS treated?
Early stage cancer treatment can be divided into two basic categories – local-regional and systemic therapies. For regional therapy, the goal is to rid the patient of the cancer such that where it was once known to be it should never recur. Local therapy is composed of usually both surgery and radiation therapy in women who desire to preserve breast tissue or a mastectomy alone. Both choices result in equivalent survival, but the mastectomy choice reduces the risk of a recurrence most maximally.
Because having LCIS in one breast raises the average risk of developing any cancer in either breast by roughly double the average rate for breast cancer for an otherwise healthy woman with limited or no excess breast cancer risk, women like Wilson often elect to undergo a bilateral mastectomy (one on the side with cancer and the other as prophylaxis).
Another option to reduce the risk of a breast cancer in the unaffected breast is to take anti-estrogen treatments, which can drastically lower the rates to those approaching or possibly better than a healthy, unaffected woman’s rate of breast cancer.
Management of the lymph nodes is typically performed by a procedure called sentinel lymph node sampling, wherein a radioactive tracer chemical and dye are injected into the breast to identify the first several lymph nodes that drain the breast tissue.
Once identified and dissected from the patient’s armpit (aka axilla), if these nodes return with pathology confirming no involvement it is safe leave the remaining nodes. On the other hand, if it is positive for cancer involvement, it is customary to remove the remaining lymph nodes to identify any additional disease that may remain.
A full node dissection as compared to a sentinel node dissection is associated with a much higher rate of post-operative lymphedema (up to 40 percent), which can be a very disabling long-term complication. The algorithm to manage the lymph node is complex and can be driven by several patient specific factors and preferences.
For Wilson, systemic therapy may also be appropriate to ensure that cells that have already escaped the breast and now reside in other parts of the body are also eliminated. Systemic therapy works exceptionally well and is life-saving when cancers are in a "micro"-metastatic state whereby a small number of cells are possibly hiding in distant tissues from the breast. The goal is cure. For systemic therapy in invasive lobular carcinoma, it is unusual to require chemotherapy unless there is extensive disease or particular pathologic characteristics. The main form of treatment is endocrine/hormone therapy.
In women who have undergone menopause, endocrine therapy involves the reduction of circulating estrogens with drugs called aromatase inhibitors and less commonly by blocking of its action on cancer cells with drugs referred to as SERMs.
In the United States, there are three commercial available aromatase inhibitors and they all work equally well and are all available as generics (less expensive). The standard duration is five years of therapy to be taken every day orally. The pills are exceptionally well tolerated by most women with the main side effects being menopause symptoms (hot flashes, night sweats, achy joints, crankiness, mood changes).
One other point with aromatase inhibitors is to consider the effect on bone. With the loss of estrogen experienced when one takes an aromatase inhibitor, over time the bones can become thin or "osteopenic." To prevent this, it is important to take vitamin D and calcium supplements if tolerated. Bones should be monitored for density using a DEXA scan periodically at the discretion of the treating physician.
Even though the main goal of endocrine therapy in early stage breast cancer is to treat disease that cannot be seen by imaging elsewhere in the body, as previously discussed above it can also eliminate precursors to cancer in any remaining breast tissue thus effectively preventing breast cancer.
Because limited information is available about Wilson’s case, it is hard to speculate on the nuances of her care or her decisions. Generally, the choices women like her face are those reviewed here. Every patient is different and should be managed as her story unfolds with thoughtful consideration to unique, individualized aspects of her care.
This story first appeared on the Seattle Cancer Care Alliance's blog.
