The following article is excerpted from Chapter Three of Advanced
Breast Cancer: A Guide to Living with Metastatic Disease, 2nd Edition,
by Musa Mayer, copyright 1998, published by O'Reilly & Associates, Inc.
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For most women with metastatic disease, however, a period of months to years, sometimes many years, elapses between primary diagnosis and the discovery of advanced disease. Recurrence, when and if it happens, may be local, regional or distant, and may be singular, involving a single site in one part of the body, or widespread, involving many lesions in several parts of the body. The extent of the disease and where it is located give some measure of how serious the prognosis may be, and how rapidly the cancer may progress. In a study of over a thousand women whose cancer had recurred, researchers found that, "Involved axillary lymph nodes at the time of initial diagnosis and/or lack of ERs (estrogen receptors) may indicate a highly malignant tumor or a weak host defense, either of which might be related to short survival after relapse." 1
Another very important prognostic factor is time to recurrence. If many years have elapsed between the initial diagnosis and recurrence, this can mean that the cancer cells are relatively slow to reproduce themselves, and have a long doubling time. Often, though not always, this indicates slow disease progression.
Still another crucial factor is whether or not the tumor needs the hormones estrogen or progesterone in order to grow. While this is not an absolute measure, a tumor can be said to be estrogen and progesterone receptor positive or negative (ER or PR + or -), depending on the findings in the initial pathology. Having an ER+ and/or PR+ tumor is thought to be a positive prognostic sign. This is because hormonal treatments can slow, stop or even regress the growth of these tumors, sometimes for long periods, before chemotherapy drugs, which are more toxic to normal body cells, have to be used.
The tumor's response to the various treatments used in metastatic breast cancer is one of the most significant factors in prolonging life. Some women's cancers are very sensitive to chemotherapy treatments, some are sensitive only to some, and still others are resistant to almost every drug. Eventually, almost all tumors mutate to become resistant to the drugs used to treat them, and will no longer respond. The oncologist's job is to determine which drugs, used in which sequence, will produce the longest partial and complete responses (remissions), combined with the best quality of life.
When I asked my oncologist, Dr. Samuel Waxman, who divides his time between research and clinical practice, to characterize how he looks at the treatment of metastatic breast cancer, he spoke of what he does as a complex and subtle process.
I try to convert the disease to a chronic condition. I've certainly had patients with advanced breast cancer for many years, in different areas, and they can live with it for a long time. We don't know why. I am sure it's not just my treatment. I am sure there are things going on that we don't know how to measure in a given patient. I don't think it's witchcraft. It's the biology of the tumor and the biology of the host. That, and the fact of the instability within the cancer cell population and its ability to become more de-differentiated and less responsive and more resistant to the treatments we use. Even a given population of cancer cells in the same patient is totally heterogeneous. That's why the problem is so complicated.
Treating this complex disease is the focus of much ongoing research, and forms a body of knowledge that is constantly changing. The standard and experimental treatments and what is known about them will be discussed in some detail in the sections on treatment.
A local recurrence can happen when tumor cells remain in the original site and, over time, grow to become a measurable tumor. While requiring further treatment, a local recurrence doesn't by itself mean the disease has become systemic and life-threatening. A percentage of women who elect to have breast conserving surgery (lumpectomy or similar limited surgery which removes the tumor and enough surrounding tissue to provide clear margins) will have some part of the tumor grow back from cancer cells that were left behind, despite radiation therapy to the remaining breast tissue. Residual cancer cells, over time, can grow a new tumor without spreading through the circulatory or lymphatic system. One extensive study, published in the Journal of Clinical Oncology, found that 10 to 20 percent of patients will have locally recurrent disease one to nine years after lumpectomy and radiation.2
Doctors generally treat local recurrence as a failure of the initial treatment, and do not consider it a true spread of the cancer. Usually treated with a "salvage mastectomy," this kind of limited recurrence is thought to have little impact on overall mortality when it is found growing in residual breast tissue contiguous to the primary tumor. Researchers have not yet determined, however, whether an invasive local recurrence in the remaining breast tissue can easily spread to other parts of the body. Though evidence is inconclusive, it is reasonable to assume that spread may be possible.
While a second primary breast cancer in the same breast may be referred to as a local recurrence, it is really a new cancer and is treated in much the same way as a new breast cancer in the other breast might be. Breast conserving surgery is not an option, however, because the breast cannot be irradiated a second time, and the risk of local recurrence is unacceptably high without radiation treatment.
After mastectomy, which always leaves some small amount of breast tissue, a local recurrence is also possible in the remaining skin and fat, and can be treated with excision and radiation if the diagnosis is clear.
The problem in this instance, though, is that sometimes a new tumor in the mastectomy scar does not arise from residual breast tissue, but from spread of cancer through the circulatory or lymphatic system. This can be a disturbing sign, because in the majority of cases it is a harbinger of systemic, metastatic disease. Unfortunately, it is not always possible to tell the difference between these two very different circumstances. "It is impossible to tell whether local recurrence results from cells that persist locally or from those that have passed through the general circulation to return to implant at a favorable site," according to Dr. Edward Scanlon.3
One day, Barbara Ragland looked in the mirror and saw something strange at the site of the scar from the Halstead radical mastectomy she'd had nineteen years before.
There was a raised bump and a short distance from that was a depression-like a hole where the skin was pulled in. It didn't dawn on me that it could be recurrence. When the internist first saw the tumors (which were obvious by just looking at my chest), she really showed concern. I thought she was just being very cautious when she ordered tests and sent me to the surgeon. I didn't think it would turn out to be cancer. I'd had annual checkups from my surgeon for nearly 20 years and the radiologist had checked me annually for 10 years. When the pathology report came back, the surgeon's nurse called me at my office. She said, "I have bad news-it's cancer." I asked which tumor was cancerous and she told me both were.
Sites of regional recurrence include the muscles of the chest wall, the internal mammary lymph nodes under the breast bone and between the ribs, and those up above the collar bone, known as supraclavicular nodes, and the nodes in the neck. The remaining skin and scar tissue can be affected as well.
A regional recurrence is considered more serious than a local recurrence, for it usually indicates that the cancer has spread past the confines of the breast and axillary lymph nodes. Here is how the Physician's Data Query of the NCI expresses these relative degrees of risk and severity: "Patients with chest wall recurrences of less than 3 cm, axillary and internal mammary node recurrence (not supraclavicular, which has a poorer survival), and a greater than 2-year disease-free interval prior to resection have the best chance for prolonged survival."4
Kim Banks was diagnosed at 32 with an aggressive two-centimeter infiltrating ductal carcinoma. Two axillary lymph nodes showed spread of the disease, so she underwent chemotherapy. She decided on a latissimus dorsi breast flap reconstruction, in which a muscle from her back was brought to the front of her body to shape a new breast.
Though her tumor tested positive for estrogen and progesterone receptors, Kim was among the minority of women who have serious side effects with the estrogen antagonist, tamoxifen. She gave up taking tamoxifen as a possible preventive agent against recurrence because it increased her migraine headaches. Two years later, the cancer was back in between her pectoral muscles in the shape of a flat coil about four inches in length. Before a course of chemotherapy could be completed, metastases to her spine were detected.
Distant recurrence or metastasis
A distant metastasis, most often to bone, bone marrow, lungs or liver, and to soft tissue and other organs somewhat less frequently, is the most alarming kind of recurrence, for it indicates that there may be more widespread dissemination of the cancer.
The liver and lungs are common metastatic sites for many cancers, probably because the role they play in purifying and nourishing the body means that these organs are highly vascular. They act as filters for the entire blood supply, which passes through them. Breast cancer also appears to be attracted to bone and bone marrow tissue when it metastasizes, a characteristic referred to as "osteotropism." The bones of the spine, ribs, pelvis and skull, and the long bones of the legs and arms are most commonly affected. Metastases to the brain and eye are not unusual, particularly as secondary sites.
A diagnosis of recurrence leaves the patient and her family in a state of shock and grief. That which has been most feared is now a reality, and the future is in question. That moment is always etched indelibly on the minds of all who experience it. Bob Crisp recalls it this way:
Ginger's diagnosis occurred on the same day as the Oklahoma City bombing, which saturated the news. Ginger saw that and knew that life could end anytime, anywhere, very unexpected. So it gave her strength that her condition was not as bad, and that, unlike those poor persons, she was still alive and there was always hope. Funny how something tragic like that might affect her and give her perspective.
- L. Schwartzberg, et al., "Prognostic factors after high-dose chemotherapy (HDC) for high-risk stage II and III breast cancer," Proc Annu Meet Am Soc Clin Oncol 14 (1995): A114.
- A. M. Huelskamp, et al., "High-dose consolidation chemotherapy for stage IIIB breast cancer in remission: Intermediate follow-up and comparison with intensively treated historical controls," Proc Annu Meet Am Soc Clin Oncol 14 (1995): A93.
- G. M. Clark, et al., "Survival from first recurrence: relative importance of prognostic factors in 1,015 breast cancer patients," J Clin Oncol 5 (January 1987): 55-61.
- A. S. Lichter, et al., "Mastectomy versus breast-conserving therapy in the treatment of Stage I and II carcinoma of the breast: A randomized trial at the National Cancer Institute," Journal of Clinical Oncology 10 (1992): 976-83.