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Treatment Options

In large part, MBC remains incurable because the cancer is able to acquire resistance to
each treatment given, as mutations occur and some cancer cells die but other more deadly
ones remain and reproduce. Thus, MBC is controlled through the use of sequential “lines” of
treatment that work in different ways.

Targeted therapies focus on genes that play dominant “driver” roles in the growth of
ER+ and/or HER2+ MBC. Use of drugs that successfully target these key drivers controls
cancer growth and extends survival. Sooner or later, however, MBC almost always acquires
resistance to a given treatment, and a treatment change is necessary. Beyond tamoxifen,
aromatase inhibitors (Arimidex, Femara and Aromasin) and fulvestrant (Faslodex) have
offered further lines of treatment for MBC patients with ER+ disease. Trastuzumab (Herceptin)
has slowed the spread of this aggressive form of MBC in the 25% of patients whose cancer is
HER2+. Continued use of drugs targeting HER2 throughout treatment results in better control
of HER2+ MBC. Newer agents targeting the HER2 pathway need to be studied further but may
extend survival, as indicated in a recent small study showing a median survival of 45 months in
patients with HER2+ MBC [101] .

It’s important to ask whether all MBC patients whose cancers are ER+ and/or HER2+ have equal
access to the multiple lines of expensive targeted treatments appropriate for their subtypes
and to the supportive follow-up care now considered standard that can greatly improve quality
of life. Cytotoxic chemotherapies in combination with HER2-directed treatments are important
to those patients with HER2+ breast cancer. Chemotherapy is the sole effective approach
so far in triple-negative (TN) MBC treatment. Over the past 2 decades, newer chemotherapy
agents have undergone reformulation and refinement to improve tolerability and therefore
improve quality of life as well, even if they do not significantly extend survival. Improved
tolerability is especially important for patients with TN MBC, for whom chemotherapy remains
the only treatment option. These kinds of quality of life improvements are not reflected in
studies that look at survival alone..

Survival

It has been suggested that outcomes of those with de novo MBC could be used to model
duration of survival for all patients with MBC, because mortality data for de novo MBC patients
are captured in the SEER registries.

However, de novo MBC patients are not necessarily representative of the entire MBC
population. This is shown in a study [102] comparing the outcomes of de novo and recurrent MBC
patients by analyzing an MD Anderson Cancer Center database of MBC patients who received
chemotherapy from 1992 to 2007. Overall, patients with recurrent MBC had a 1.75 increased risk
of death (median survival, 27 months) compared with de novo MBC patients (median survival,
39 months). In the recurrent MBC group, several factors predicted longer survival: initial
diagnosis at stage I, presence of HER2+ disease, low-grade tumors, no prior chemotherapy,
and a longer disease-free interval after adjuvant treatment. It should be noted that survival
was longer for patients who were white (vs. other race or ethnic group), premenopausal (vs.
postmenopausal), had ER+ MBC (vs. other types), or had only 1 (vs. >1) bone metastasis.
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One reason for the difference in survival may be that the patients with de novo MBC had not
been exposed to any breast cancer treatments at the time of diagnosis, and consequently had
not acquired resistance to therapy, leading to better and longer responses to treatment as
compared with the recurrent MBC patients.