Systemic Treatment for Metastatic Breast Cancer
By Diane Roth, September 23, 2012
What Is Metastatic Breast Cancer?
Metastatic Brest Cancer (MBC) is sometimes called stage IV breast cancer, or advanced breast
cancer. Metastatic breast cancer is breast cancer that has migrated from the breast to a distant
site n the body (commonly bones, lungs, liver and sometimes the brain). Even though the breast
cancer is no longer confined to the breast, it is still called breast cancer, (not liver cancer if it is in
the liver) as the breast was the primary site of the cancer. That being said, metastatic breast
cancer is treated with a variety of approved breast cancer drugs. Diagnostics may show one site
of metastatic spread, but typically once one site is visible, there is likely spread to other sites
that is not yet being detected by imaging , so systemic treatment is the treatment of choice for
MBC, as it treats all the cancer cells in the body, not just those than can be detected. Treating
metastatic breast cancer means careful consideration of a woman’s type of cancer, what type of
treatment was given at diagnosis, the extent of the cancer, and quality of life issues that should
be discussed with her physician. Sometimes symptoms need to be addressed first, before
systemic therapy or in combination, to help with pain. These therapies can include radiation and
pain medication.
Systemic Treatments for MBC include:
 Hormonal therapy, with drugs that shut down the estrogen feeding the cancer
Endocrine therapy is indicated in ER/PR+ MBC as first line treatment. In ER/PR+ breast
cancer, the tumor is being driven primarily by estrogen, and these treatments target the
receptor that is receiving the estrogen and shut is down, essentially starving the tumor of
what it needs to grow. Treatments choices will depend on the previous treatment a patient
has received.
Ex. SERMs, Selective Estrogen Modulators (Tamoxifen)
AIs, Aromatase Inhibitors ( anastrozole, extemesane, or
letrezole)
Pure antiestrogens (Fulvestrant)
One of the problems with endocrine therapy is endocrine resistance. After extended periods of
treatment, the cancer cells stop responding to treatment and the cancer begins to progress.
Research on endocrine resistance is paying off!
New in the area of of endocrine therapy is the drug Everolimus (Afinitor). Everolimius is an
mTOR inhibitor; m TOR plays a role in cell proliferation, so to block it, or inhibit it, stops
proliferation. Everolimus has been shown in trials to be very effective at overcoming endocrine
resistance, providing another option for patients who have developed resistance. The BOLERO2
trial showed that Everolimus, in combination with exemestane, (AI) more than doubles PFS
(progression free survival). A down side of this exciting news is that adding Everolimus to an AI
made side effects increase. These included stomatitis (mouth sores), fatigue, diarrhea, and rash.
Theses side effects were manageable by reducing doses, and treating symptoms.

Chemotherapy or Cytotoxic Therapy
Chemotherapy drugs slow or stop the growth of cancer. They are
given alone, in sequence or in combination, depending on the nature
of the patient’s disease, and choices made by the patient and her
physician
A note about Chemotherapy for TNBC (triple negative breast cancer).
Triple negative breast cancer is a very heterogeneous disease. Currently, prognosis for TNBC is
assessed by the usual variables (TNM) and TNBC is treated like any other invasive breast cancer.
Both known subsets of TNBC, basal and claudin-low, are very sensitive to conventional
chemotherapies. There is a question about how to treat early stage, T1a, T1b node negative
TNBC, but the general feeling is that these diagnoses probably don’t warrant chemotherapy,
unless a predictive/prognostic assay shows high risk of recurrence. We are all watching with
hopeful intent, for the information that genomics will bring us regarding TNBC and how to best
treat it.

Biologic Therapy or Targeted Therapy
Drugs that target a specific protein or feature of the cancer to stop
cancer progression (Hercpetin which targets the Her2 protein,
or Avastin which targets angiogenesis).
New in the treatment of Her2+ MBC, is the monoclonal antibody Pertuzumab (Perjeta)
given along with Trastuzumab (Herceptin) and docetaxel (Xeloda) approved by the FDA in
2012 for the first line treatment of HER2+ MBC. The stunning results of the CLEOPATRA
trial, which looked at Pertuzumab in combination with Trastuzumab and docetaxel vs
Trastuzumab and docetaxel alone, the patients receiving Pertuzumab had an increased PFS
of 18 months, the largest gain ever seen in a trial. The trial showed that a dual blockade of
the HER family of receptors was far superior to the single antibody.
Also of great interest is T-DM1, the monoclonal/drug conjugate. The Her2 antibody
(Herceptin) carries the drug (metansine) into the cell and delivers it there, providing the
benefit of both antibody and cytotoxic drug, achieving more cell kill, and fewer side effects.
T-DM1 is expected to be approved by the FDA late this year or early next year. The results of
the EMELIA trial showed significant improvement in OS and PFS for patients receiving TDM1. T-DM1 will most likely benefit patients who are progressing on Herceptin.
So here is what a possible treatment plan might look like by next year, for HER2+ MBC…
First line, Pertuzumab with Trastuzumab and any taxane…Second line, Pertuzumab and
Trastuzumb….Third line, T-DM1….and fourth line, Lapatinib with capecitibine.

Bone modifying agents
Bisphosphonates
Support bone strength, reduce fractures, prevent hypercalcemia,
Spinal cord compression, and possibly prevent metastases
Finally, a brief word about clinical trials. Clinical trials benefit everyone. Patients receive the
highest standard of care and follow-up, while possibly benefitting from some of the amazing
new drugs being tested. Physicians learn how to best treat patients, and all cancer patients
benefit from the results. Most clinical trials focus on patients with MBC, because that is the
population where the results can be seen and measured most clearly. You will never be
UNDER treated in a trial. Patients considering trials should discuss the issue early with their
physician, as finding the right trial for you, and enrollment take some time. Trials can be
searched according to diagnosis, at nih.gov.
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