When breast cancer cells spread from the primary tumor in the breast through the lymphatic system or the circulatory system to other parts of the body, establish themselves there, and begin to multiply, they are said to have metastasized. Most cancer deaths are due to the effects of metastases resistant to treatment. Metastases must find favorable conditions to grow. According to Drs. Lee Ellis and Isaiah Fidler, "To grow beyond the size of 1-2 mm., primary tumours and metastases must develop an adequate blood supply through the process known as angiogenesis." ¹

"The process of metastasis isn't random," explains Dr. Loren Buhle, creator of the Oncolink Cancer Information Service at the University of Pennsylvania. "Instead, it is a cascade of linked sequential steps that must be traversed by the tumor cells if a metastasis is to develop. Each step involves multiple tumor-host interactions. To be successful, a metastatic tumor cell must leave the primary tumor and invade local host tissue. It must then enter the circulation, survive in the circulation, arrest at the distant vascular bed, extravasate (or spread) into the organ intersitium (space between the organs) and/or parenchyma (the organ itself) and multiply to initiate a metastatic colony. Interruption of the metastatic cascade at any of these steps can prevent the production of clinically symptomatic metastasis."²

Micrometastases, presumed "seeds" from the primary tumor that later grow into tumors at distant sites, are still too small to find on any scan or blood test. Often, it will be years before these new tumor sites grow large enough to be detectable. The rate of growth, or "doubling time," of a cancer is not necessarily constant, either. Sometimes, metastatic tumors will lie dormant or quiescent, until, for reasons as mystifying as the reasons they became dormant in the first place, the tumors begin to grow again. At other times, the disease progresses rapidly and relentlessly.

While the pathophysiology of metastasis is beyond the scope of this book, some general observations may be helpful. According to Dr. Alan Aaron, the two theoretical models that have been most frequently cited in discussing advanced breast cancer are the "anatomic-mechanical" theory proposed by J. Ewing in 1928, and the "seed and soil hypothesis" proposed by Paget in 1889. "The mechanistic approach states that metastasis develops in the first organ a tumor cell encounters."³ As Dr. Aaron observes, this theory, while it clearly plays a role, has been shown to be oversimplified, and has given way to a second theory, known as "chemotaxis," based on the Paget hypothesis, meaning that cancer cells are chemically attracted to certain specific sites within the body.

Some scientists now believe that this happens because of certain molecular patterns on the surface of cells, as pathologist Dr. Erkki Ruoslahti explains:

Physical trapping of cancer cells in the blood vessels at the site of metastasis is not the whole story, however. If it were, cancers would not spread so diversely through the body. Indeed, some types of cancer show a striking preference for organs other than those that receive their venous blood-witness the tendency of metastatic prostate cancer to move into the bones. Once again, the explanation seems to rest with the molecular address system on cell surfaces. A specific affinity between the adhesion molecules on cancer cells and those on the inner linings of blood vessels in the preferred tissues could explain the predilection of the cells to migrate selectively. Different concentrations of growth-promoting factors and hormones in various tissues may also play a part.⁴

When you are diagnosed with primary breast cancer, particularly if the tumor is in the upper, outer quadrant of the breast-the part of your breast nearest to your arm-it is likely to spread, if it spreads at all, first to the axillary lymph nodes under your arm, which are the nearest nodes that drain the lymphatics in this part of the breast. This is, of course, why these lymph nodes are biopsied at the time of surgery, so that determining the extent of disease can suggest optimal treatment. The cancer may be contained there, or micrometastases may escape and begin to establish themselves elsewhere.

This isn't always the route of spread, by any means. If your tumor was located more centrally in the breast, under the nipple, or in the inner quadrants, you may experience an undetected spread to the internal mammary nodes located between the ribs and beneath the sternum. Doctors used to believe that cancer always spread through the lymphatic ducts, beginning in the breast and radiating outwards. Now we know that isn't always true, for nearly 30 percent of women with no cancer evident in their lymph nodes following axillary dissection eventually go on to develop metastatic disease. Clearly, the cancer can spread microscopically through the bloodstream and perhaps even pass through the lymphatic system without detection. Your cancer may already have been systemic-that is, affecting your whole body-by the time you were first diagnosed. This is the rationale behind giving strong chemotherapy to women with large, or rapidly dividing tumors, particularly those younger women whose tumors are not estrogen or progesterone receptor positive, or who have several or many lymph nodes affected. Since chemotherapy is most likely to be effective the first time around, as adjuvant treatment following primary diagnosis and surgery, oncologists will try to identify those women at highest risk for recurrence, using the best tests and prognostic indicators available, so that these high-risk patients may receive the best available prophylactic, or preventative, treatments.

At the time of this writing, physicians and patients are hopeful that high-risk women with Stage IIB and Stage III diagnoses and ten or more positive axillary lymph nodes will have extended disease-free survival from high-dose chemotherapy with stem cell or bone marrow rescue, but the results of these studies are not yet in. Two large scale studies, undertaken by the Cancer and Leukemia Group B (CALGB), the Eastern Cooperative Oncology Group (ECOG) and the Southwest Oncology Group (SWOG), are comparing this treatment with conventional chemotherapies and, as of this writing, are still enrolling patients. Preliminary results appear to indicate some success. ⁵

Many stories, common threads

Yet there are common threads. The ways that people effectively come to terms with life-threatening illness suggest shared themes and concerns. More universal-and more crucial in your life than any of the specific details of the disease onset-is the emotional impact of such a diagnosis, and the struggle, confusion and ultimate decisions that go into seeking out the best doctors and making good treatment choices. This material will be covered in the next chapters.

Reading about the disease in all its manifestations is emotionally trying. As you read, please keep in mind that every one of these people recovered from the brutal shock of her diagnosis, reported here and in the next chapter, and went on to find effective ways of coping with the progression of the disease and its emotional impact.

Primary diagnosis: Stage IV

Kathy Stone, 53, a former fiscal administrator for the University of California before her disability retirement, lives with her husband Chuck, a retired fire marshal, in a community near San Francisco. Together, they've raised two sons and two daughters, all grown and out in the world, and have four grandchildren, two of them teenagers.

In July 1994, several carcinomas were found in Kathy's left breast, along with a patch of inflammatory cancer. All 28 axillary nodes were affected, and there was cancer in the supraclavicular lymph nodes under her collar bone, so the cancer was said to have metastasized already. In August of 1995, after a year of treatment, widespread new metastases were found in her femur, hip, pelvis, sacrum, spine, ribs and cranium, as well as a soft tissue tumor in the lymph nodes in her neck.

Eight months later, this is what Kathy wrote one of the newcomers on the Breast Cancer Discussion List:

I, too, was diagnosed as Stage IV from the onset, and it scared the shit out of me, but I have started living each day and stopped getting ready to die. I have decided that whatever takes me and whenever it is will still be a mystery to me. None of us is guaranteed the next moment.

Barb's oncologist told her that all of the 12 lymph nodes sampled showed spread of her cancer. One particular word stuck in her mind from this conversation. "He told me my prognosis was 80 percent failure," she recalls. "What the hell did he mean by failure? Failure equals death? The doctor ordered an MRI of my brain, and a CT scan of my chest, explaining that there was an excellent chance of mets (metastases), and they had to search to see where." The tests showed cancerous lesions in her liver and spine.

Nancy Gilpatrick, 43, a social worker on leave from her private practice, who was living with her boyfriend in Utah, was diagnosed with breast cancer in November of 1995. Stunned as she was by the diagnosis, it never occurred to her that the hip pain she'd been experiencing for two months could be a bony metastasis of her breast cancer. Sudden, increased pain turned out to be a fracture of the pubic bone. In March of 1996, Nancy reported, "I had another bone scan and CT of the abdomen. There was new disease and the original tumors looked like they had grown. This was only a few months from the original tests. I was dealing with an incredibly aggressive cancer." One month later, a fracture to her left hip forced her to use a walker and wheelchair. She was told she would have to wait until the effects of her high-dose chemotherapy subsided enough for her to heal from surgery required to repair her pelvis and hips. "I have not had one doctor's visit since the diagnosis that was positive," she exclaimed in pained frustration.

Pam Hiebert, 49, an electronic publishing technician, lives with her life partner, Sylvan, in Oregon. In 1993, Pam was diagnosed with a hormone sensitive breast cancer that had already spread to her left femur and one rib. Her disease was stabilized with tamoxifen for three years. On a first name basis with her oncologist, Pam re-read her chart of the first days after her initial diagnosis. "Ralph ended his summary of my condition and prognosis by writing, 'This patient is going to be very difficult to keep alive.' I beat his odds!"

But spring of 1996 brought stiff necks, headaches, and a rise in tumor markers. Awaiting new tests, Pam wrote in her journal:

Tomorrow is just the mechanics of a procedure. I have the same amount of hours in this day as I would ever have. Use your day well and let others do their job. They can't pass a verdict on you. You are of free will. You live the life meant for you. Live the moment. Love the moment.

What if they find something and it's bad?
What if I don't have a lot of time left?
What if they want to push ahead to high-dose?
Who will I be?
What if they find nothing new?
and they just shrug?
What if I just let go... returned to work...
To think about the summer?
What if I rush to fill my tamoxifen Rx again?
Who will I be?

What am I now that I won't be tomorrow?
Except more knowledgeable.

Notes

1. Ellis, Lee N., and Isaiah J. Fidler, "Angiogenesis and breast cancer metastasis," The Lancet 346 (Aug 95):388.
2. Loren Buhle, Personal communication (August 3, 1996).
3. Alan D. Aaron, "The management of cancer metastatic to bone," JAMA 272 (Oct 94):1206.
4. Erkki Ruoslahti, "How Cancer Spreads," Scientific American (Sep 96).
5. Hurd, D. D., and W. P. Peters, "Randomized, comparative study...for patients with operable stage II or III breast cancer involving 10 or more axillary lymph nodes," J Natl Cancer Inst Monogr 19 (1995):41-44.