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More knowledge needed onmolecular subtypes of ER positivity in
metastatic breast cancer
R
esults of a single-centre retrospective
study have shown that most subgroups
of patients with metastatic breast
cancer who were positive for oestrogen and/
or progesterone receptors responded well to
endocrine therapy. Only three small groups,
however, responded at 100%.
These findings point to a need for more
knowledge of molecular subtypes of oestrogen
receptor positivity in metastatic breast cancer.
Marie Sundqvist, MD, of the Kalmar County
Breast Unit, Sweden, explained that patients
with oestrogen/progesterone receptor-
positive, distant metastatic breast cancer
often, but not always, respond to endocrine
treatment.
Also, the time to treatment failure varies
widely. Dr Sundqvist set out to determine
whether predictive factors of response to
endocrine therapy could be identified from
tumour and patient characteristics.
Dr Sundqvist said, “Guidelines recommend
endocrine therapies as first-line treatment in
metastatic, oestrogen and/or progesterone
receptor-positive breast cancer except in
cases of visceral crisis. The implementation
of guidelines is variable, however. We wanted
to explore response patterns in a consecutive
population, to assess the value of endocrine
therapy and identify subgroups with more or
less benefit from endocrine therapy.
All patients who had been treated for
oestrogen- and/or progesterone receptor-
positive, distant metastatic disease during the
prior 15 years were identified and tumour data,
treatments, and responses were recorded.
In most cases, oestrogen and progesterone
receptor, as well as HER2 assessments were
performed in the metastasis, but in these
cases, status of the primary tumour was used.
A total of 246 patients with oestrogen and/or
progesterone-positive disease were identified.
Most patients had received palliative
endocrine treatment and chemotherapy
sequentially, but 72 had been treated with
hormonal agents only.
Thirty-five patients had never received
endocrine therapy. Time to treatment failure
for each endocrine regimen was calculated
and summoned for each patient to receive
a cumulative response time to endocrine
therapy.
Histological grade and type of primary
tumour, oestrogen and/or progesterone
receptor and HER2 status, site of presenting
metastases, and patient age at diagnosis were
then correlated with the radiotherapy result.
Response to treatment was defined as partial
regression or stable disease after more than 3
months of therapy.
A total of 206 patients had received one to
six different endocrine regimens. Eighty-five
percent of patients responded to treatment
for 3–250 months, median 27 months.
Thirty-two patients responded to endocrine
treatment, 26 of whom exhibited strong or
medium expression of oestrogen receptors.
Three groups of patients responded at 100%
to endocrine therapy; grade 1, mucinous
and tubular mixed tumours. Median age
of patients who received endocrine and
chemotherapy sequentially was 54 years. Of
those who received endocrine therapy only,
median age was 65 years. Patients 40 years
of age or younger at the time of diagnosis, at
88%, responded as well as those older than
60 years.
HER2-amplified tumours responded at 75%
to endocrine therapy without trastuzumab.
Maximum response time was 154 and median
34 months. Only two subgroups performed
significantly worse than others.
Patients with oestrogen receptor-negative,
progesterone receptor-positive tumours
experienced a 56% response rate and those
presenting with liver metastasis, a 50%
response rate. Median response time for both
cohorts was only 6 months.
Dr Sundqvist said, “We also compared
patients who received endocrine therapy
and chemotherapy sequentially. The median
cumulated response time to chemotherapies
was less than that to endocrine therapies, as
was the maximum response time”.
“For instance,” she added, “the cumulated
response time to endocrine therapies for grade
3 (fast proliferating) tumours was 23 months
and maximum response time 81 months,
while response to chemotherapies was 12
and 66 months, respectively. The more slowly
proliferating grade 1 tumours responded at
median of 43, maximum 215 months, to
endocrine therapies but only 12 and 24
month, respectively, to chemotherapies.”
Dr Sundqvist said that, although most patient
subgroups responded well to endocrine
therapy, only three small groups responded
at 100%. To optimally tailor endocrine
treatment in metastatic breast cancer, more
knowledge of the molecular subtypes of
oestrogen receptor positivity is needed.
The results support the assertion that
patients presenting with hepatic metastasis
and those with oestrogen receptor-negative,
progesterone receptor-positive tumours
should not receive endocrine therapy as their
first line of treatment.
“An important finding,” said Dr Sundqvist,
“is that fast-proliferating grade 3 cancers and
young patients respond very well to endocrine
therapy as well as HER2-positive patients.”
She added, “Hopefully in the future, studies
of the molecular biology of metastases will
enable more exact identification of which
tumours will vs will not respond to endocrine
therapy.”
PracticeUpdate Editorial Team
An important finding is that
fast-proliferating grade 3
cancers and young patients
respond very well to
endocrine therapy as well as
HER2-positive patients.
© ECCO2017 European Cancer Congress
ECCO2017
15
VOL. 2 • NO. 2 • 2017