Researchers are studying how molecular subtypes of breast cancer may be useful in planning treatment and developing new therapies.
Most studies divide breast cancer into four major molecular subtypes:
These subtypes also appear in ductal carcinoma in situ (DCIS) [37-38].
There are other less common molecular subtypes, including claudin-low and molecular apocrine types. At this time, molecular subtypes are used mostly in research settings and are not included in pathology reports (learn more). Prognosis and treatment decisions are still guided mainly by tumor stage, tumor grade, hormone receptor status and HER2 status.
The complex profile of each subtype is determined using molecular and genetic information from tumor cells.
However, some characteristics (including hormone receptor status, HER2 status and proliferation rate) can be used to roughly define the four major subtypes (see Figure 4.9 below).
Much of what is known about the four subtypes is related to these characteristics that are already well understood.
These tumors tend to be*
*These are the most common profiles for each subtype. However, not all tumors within each subtype have all these features.
ER-positive = estrogen receptor-positive
ER-negative = estrogen receptor-negative
PR-positive = progesterone receptor-positive
PR-negative = progesterone receptor-negative
HER2-positive = HER2 receptor-positive
HER2-negative = HER2 receptor-negative
Adapted from selected sources [39-43].
Learn more about hormone receptor status (estrogen receptor status and progesterone receptor status).
Learn more about HER2 status.
Most breast cancers are luminal tumors. Luminal tumor cells look the most like cells of breast cancers that start in the inner (luminal) cells lining the mammary ducts.
Luminal A tumors tend to be:
Fewer than 15 percent of luminal A tumors have p53 gene mutations, a factor linked with a poorer prognosis [42,44].
Of the four subtypes, luminal A tumors tend to have the best prognosis, with fairly high survival rates and fairly low recurrence rates [40-42,45-46].
Because luminal A tumors tend to be ER-positive, treatment for these tumors often includes hormone therapy (learn more).
Luminal tumors have cells that look like those of breast cancers that start in the inner (luminal) cells lining the mammary ducts.
Luminal B tumors tend to be:
Women with luminal B tumors are often diagnosed at a younger age than those with luminal A tumors [46-47].
Compared to luminal A tumors, they also tend to have factors that lead to a poorer prognosis including [40-42,44,46-48]:
Some (about 30 percent) luminal B tumors contain p53 gene mutations .
Women with luminal B tumors tend to have fairly high survival rates, although not as high as those with luminal A tumors [41,46].
Triple negative breast cancers are:
There are several subsets of triple negative breast cancer. One subset is referred to as basal-like because the tumors have cells with features similar to those of the outer (basal) cells surrounding the mammary ducts. Most basal-like tumors contain p53 gene mutations [42,44].
Most triple negative tumors are basal-like and most basal-like tumors are triple negative. However, not all triple negative tumors are basal-like and not all basal-like tumors are triple negative (as shown in the figure below).
About 15 to 20 percent of breast cancers are triple negative or basal-like [39-44,49].
These tumors tend to occur more often in younger women and African-American women (more on race/ethnicity and subtypes of breast cancer) [42,47,49-50]. Some findings suggest may also be more common among Hispanic women compared to white women [43,50].
Most BRCA1-related breast cancers are both triple negative and basal-like [42,51-52].
Triple negative/basal-like tumors are often aggressive and have a poorer prognosis (at least within the first five years after diagnosis) compared to the ER-positive subtypes (luminal A and luminal B tumors) [40,42,53]. However, after five years, this difference begins to decrease and eventually goes away [9,28].
Learn more about BRCA1 gene mutations.
Even though triple negative/basal-like tumors are aggressive, they can be treated successfully. They are usually treated with some combination of surgery, radiation therapy and chemotherapy. These tumors cannot be treated with hormone therapy or trastuzumab (Herceptin) because they are ER-negative and HER2-negative.
While targeted therapies for triple negative/basal-like tumors do not yet exist clinical trials studying treatment options are currently underway.
Potential targets for future therapies include the epidermal growth factor receptor, aB-crystallin and androgen receptor .
Learn more about triple negative breast cancer.
Learn more about clinical trials for people with triple negative/basal-like breast cancers.
Learn about research we are funding to study triple negative breast cancer.
Learn More | Current Article
The molecular subtype HER2 type is not the same as HER2-positive and is not used to guide treatment. Although most HER2 type tumors are HER2-positive (and named for this reason), about 30 percent are HER2-negative .
HER2 type tumors tend to be [40-42,44,46]:
About five to 15 percent of breast cancers are HER2 type [40,42]. About 75 percent of these tumors contain p53 gene mutations [42,44].
Women with HER2 type tumors may be diagnosed at a younger age than those with luminal A and luminal B tumors .
HER2 type breast cancers that are HER2-positive can be treated with anti-HER2 drugs such as trastuzumab (Herceptin).
Before these drugs were available, HER2 type tumors had a fairly poor prognosis [40,54].
Prevalence rates of some subtypes of breast cancer differ by race.
In studies of U.S. and British women, triple negative/basal-like tumors appear to be more common among black women (especially before menopause) compared to white women [42,47,49,50]. Some findings suggest they may also be more common among Hispanic women compared to white women [43,50]. Although the reasons for this are not clear, lifestyle factors may play a role (learn more).
Prevalence rates of luminal B and HER2 type tumors do not appear to differ by race .
Higher rates of triple negative/basal-like tumors may explain, to some degree, the poor prognosis of breast cancers diagnosed in younger black women.
Also, luminal A tumors, which have the best prognosis of the subtypes, occur less often in premenopausal African-American women compared to postmenopausal African-American women and compared to white women of either menopausal status .
*Please note, the information provided within Komen Perspectives articles is only current as of the date of posting. Therefore, some information may be out of date at this time.
Triple Negative Breast Cancer
Research Fast Facts: HER2-Positive Breast Cancer
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