The following article is excerpted from Chapter Three of
Advanced Breast Cancer: A Guide to Living with Metastatic Disease
by Musa Mayer, copyright 1998, published by O'Reilly & Associates,
Inc. For book orders/information, call 1-800-998-9938. Permission is granted
to print and distribute this excerpt for noncommercial use as long as
the above source is included. The information in this article is
meant to educate and should not be used as an alternative for
professional medical care.
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."
"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
Having spoken of the variability of metastatic disease, let's take a look at
the few generalizations about the spread of breast cancer that we can make.
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.
Many stories, common threads
The stories you are about to read represent some of the diverse ways in which
recurrent breast cancer can present itself. As you will see, these stories
differ greatly in the details of illness onset, and are as unique as are the
people afflicted. The timing of the disease, the organ systems affected, the
physical manifestations, and even the means of discovery, all varies greatly.
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
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
In about 10 percent of primary breast cancer cases, the cancer is found to have
already metastasized to distant sites when the diagnosis is first made. Doctors
refer to this as Stage IV breast cancer. Patients diagnosed this late in the
disease process often experience a rapid progression of the disease that is
difficult to gain control over. Still, they can sometimes be treated to
partial or complete remission, particularly if the disease is still very
limited and hormonally responsive.
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.
At the time of her diagnoses in October of 1995, Barb Clabo, 47, a computer
operator, and her husband, Glenn, a business manager for the Naval Sea Systems
Command, lived in Northern Virginia, with their 19-year-old son, Chad, and
their daughter, Jamie, in college nearby.
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.
And later, the same day, further self-inquiry in the form of a poem:
What if they find something and it's bad?
The scans brought certain knowledge of the end of remission and evidence of
further spread to her bones, and a change to a new hormone, Arimidex.
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.
- Ellis, Lee N., and Isaiah J. Fidler, "Angiogenesis and breast cancer
metastasis," The Lancet 346 (Aug 95):388.
- Loren Buhle, Personal communication (August 3, 1996).
- Alan D. Aaron, "The management of cancer metastatic to bone,"
JAMA 272 (Oct 94):1206.
- Erkki Ruoslahti, "How Cancer Spreads," Scientific American
- 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.