Researchers are studying how molecular breast cancer subtypes may become useful in planning treatment and developing new therapies. Most studies divide breast cancer into four major molecular subtypes:
- Luminal A
- Luminal B
- Triple negative/basal-like
- HER2 type
These same subtypes also appear in ductal carcinoma in situ [37-38].
Other less common molecular subtypes have also been described including normal breast-like, apocrine molecular type and claudin-low type. Breast cancers that do not fall into any of these subtypes are often listed as unclassified.
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 by tumor stage, hormone receptor status and HER2/neu 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/neu 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.
Figure 4.9
Subtype
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These tumors tend to be*
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Prevalence (approximate)
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Luminal A
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ER+ and/or PR+, HER2-, low Ki67
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40%
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Luminal B
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ER+ and/or PR+, HER2+ (or HER2- with high Ki67)
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20%
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Triple negative/basal-like
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ER-, PR-, HER2-, cytokeratin 5/6 + and/or HER1+
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15-20%
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HER2 type
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ER-, PR-, HER2+
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10-15%
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*These are the most common profiles for each subtype. However, not all tumors within each subtype will have all these features.
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Adapted from selected sources [29,38-42].
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Learn more about hormone receptor status (estrogen receptor status and progesterone receptor status).
Learn more about HER2/neu status.
Luminal A
Most breast cancers are luminal tumors. Luminal tumor cells look the most like the cells of breast cancers that start in the inner (luminal) cells lining the mammary ducts.
Luminal A tumors tend to be:
- Estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)
- HER2/neu-negative (HER2-)
- Low or moderate tumor grade
Only about 12 to 15 percent of luminal A tumors have p53 mutations, a factor linked with a poorer prognosis [29,43].
Of the four subtypes, luminal A tumors tend to have the best prognosis, with fairly high survival rates and fairly low recurrence rates [29,41-42,44-45]. Because luminal A tumors tend to be hormone receptor-positive, treatment for these tumors often includes hormone therapy (learn more).
Luminal B
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:
- Estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)
- Highly positive for Ki67 (have a high number of cancer cells actively dividing) and/or HER2/neu-positive (HER2+)
Women with luminal B tumors are often diagnosed at a younger age than those with luminal A tumors [44,46]. And, compared to luminal A tumors, they tend to have factors that lead to a poorer prognosis including [29,41-44,46]:
- Poorer tumor grade
- Larger tumor size
- Lymph node-positive
- p53 gene mutations (about 30 percent)
In some studies, women with luminal B tumors have fairly high survival rates, although not as high as those with luminal A tumors [29,44].
Triple negative/basal-like
Triple negative breast cancers are:
- Estrogen receptor-negative (ER-)
- Progesterone receptor-negative (PR-)
- HER2/neu-negative (HER2-)
Basal-like tumors have cells with features similar to those of the outer (basal) cells lining the mammary ducts. Basal-like tumors tend to express HER1 and/or cytokeratin 5/6 proteins and most contain p53 mutations [29,38,43,47].
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 [29,38-43]. These tumors tend to occur more often in younger women and African American women (more on race/ethnicity and subtypes of breast cancer) [29,46-51]. And, most BRCA1 breast cancers are both triple negative and basal-like [47,52-53].
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 estrogen receptor-positive subtypes (luminal A and luminal B tumors) [29,38,41-42,54].
Learn more about BRCA1 mutations.
Treatment of triple negative/basal-like breast cancer
Triple negative/basal-like tumors are usually treated with some combination of surgery, radiation therapy and chemotherapy. These tumors cannot be treated with hormone therapies or trastuzumab (Herceptin) because they are hormone receptor-negative and HER2/neu-negative.
The genes linked to basal-like tumors are not well understood at this time and thus, targeted therapies do not yet exist. However, potential targets for future therapies include the EGF receptor, aB-crystallin and cyclin E [55].
Clinical trials studying treatment options for triple negative/basal-like tumors are underway. Learn more about clinical trials for people with triple negative/basal-like breast cancers.
Learn about Susan G. Komen for the Cure’s® work with the Triple Negative Breast Cancer Foundation (TNBC) and research we are funding to study triple negative breast cancer.
HER2 type
HER2 type tumors are named for their HER2/neu-positive status. They tend to be [29,41-44,56]:
- Estrogen and progesterone receptor-negative (ER-/PR-)
- Lymph node-positive
- Poorer tumor grade
About 10 to 15 percent of breast cancers have this molecular profile [29,39-42]. About 75 percent of HER2 type tumors contain p53 mutations [29,43,56].
HER2 type tumors have a fairly poor prognosis and are prone to early and frequent recurrence and metastases [29,41-42,44-45,48-49,57]. Women with HER2 type tumors appear to be diagnosed at a younger age than those with luminal A and luminal B tumors [40-41].
HER2/neu-positive tumors can be treated with the drug trastuzumab (Herceptin).
Normal breast-like
A less common molecular subtype of tumor is normal breast-like. Although called “normal breast-like”, these tumors are not the most common type of breast cancer.
About six to 10 percent of all breast cancers fall into the normal breast-like category [29,40]. These tumors are usually small and tend to have a good prognosis [29]. Some researchers question whether these tumors are a distinct molecular subtype. It may be that some tumors are unable to be classified into another subtype because the tissue sample tested did not contain enough cancer cells.
Race/ethnicity and subtypes of breast cancer
The prevalence rates of the four subtypes of breast cancer appear to differ by race.
In studies of women in the United States and Britain, triple negative/basal-like tumors appear to be more common among black women, especially those who are premenopausal, compared to white women [29,49-51,58-60]. Although the reasons for this are not clear, some studies suggest lifestyle factors might play a role. Some findings show African American women tend to have lower rates of breastfeeding and to carry excess weight in the abdomen area compared to other women, all of which may increase the chances of having triple negative/basal-like tumors [49,57,61-64].
Higher rates of triple negative/basal-like tumors may explain, to some degree, the poor prognosis of breast cancers diagnosed in younger black women. Further, luminal A tumors, which have the best prognosis of the subtypes, occur less often among premenopausal African American women compared to postmenopausal African American women and compared to white women of either menopausal status [29].
Luminal B and HER2 type tumors do not appear to differ by race [29].
Updated 10/29/12
