Molecular Subtypes of Breast Cancer

Researchers are studying how molecular subtypes of breast cancer may be useful in planning treatment and developing new therapies.

The complex profile of each subtype is determined using molecular and genetic information from tumor cells.

Most studies divide breast cancer into 4 main molecular subtypes:

• Luminal A
• Luminal B
• Triple negative/basal-like
• HER2-enriched

These subtypes also appear in ductal carcinoma in situ (DCIS) [45].

There are many other less common molecular subtypes, including claudin-low and molecular apocrine types.

How are molecular subtypes used?

Molecular subtypes are used mostly in research settings and are not part of a standard breast cancer diagnosis.

The molecular subtype of your tumor is not part of your pathology report and is not used to guide your treatment.

Prognosis (chance of survival) and treatment decisions are guided mainly by tumor stage, tumor grade, hormone receptor status and HER2 status.

Luminal A

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:

• Estrogen receptor-positive (ER-positive)
• HER2 receptor-negative (HER2-negative)
• Tumor grade 1 or 2

About 40 percent of breast cancers are luminal A tumors [46-48].

Of the 4 major subtypes, luminal A tumors tend to have the best prognosis (chance of survival), with fairly high survival rates and fairly low recurrence rates [46-51].

Luminal B

Luminal tumor cells look like the cells of breast cancers that start in the inner (luminal) lining the mammary ducts.

Luminal B tumors tend to be ER-positive. They may be HER2-negative or HER2-positive.

Women with luminal B tumors are often diagnosed at a younger age than those with luminal A tumors [49,51].

Compared to luminal A tumors, luminal B tumors tend to have factors that lead to a poorer prognosis including [46-49]:

• Poorer tumor grade
• Larger tumor size
• Lymph node-positive

About 15-20 percent of breast cancers are luminal B tumors [46-48].

Women with luminal B tumors tend to have fairly high survival rates, although not as high as those with luminal A tumors [48-50].

Triple negative/basal-like

Triple negative breast cancers are:

• Estrogen receptor-negative (ER-negative)
• Progesterone receptor-negative (PR-negative)
• HER2-negative

Basal-like tumors have cells that look similar to those of the outer (basal) cells surrounding the mammary ducts.

Most triple negative tumors are basal-like (see figure below).

 

 

About 15-20 percent of breast cancers are triple negative/basal-like [46-48,52-54].

These tumors tend to occur more often in [51-56,59-61]:

• Younger women
• People with an BRCA1 inherited gene mutation (if you’re diagnosed with TNBC at age 60 or younger, the National Comprehensive Cancer Network recommends you get genetic testing)
• Black, non-Hispanic Black and African American women (more on race/ethnicity and subtypes of breast cancer)

Triple negative tumors may also be more common among Hispanic women compared to some other women [54,57-58].

Learn more about BRCA1 inherited gene mutations.

Prognosis (chance of survival)

Triple negative/basal-like tumors are often aggressive and have a poorer prognosis compared to the ER-positive subtypes (luminal A and luminal B tumors) [46,48,50,53].

However, they can be treated effectively.

Learn more about triple negative breast cancer, including prognosis and treatment.

Learn about clinical trials for people with triple negative/basal-like breast cancers.

HER2-enriched

The molecular subtype HER2-enriched is not the same as HER2-positive and is not used to guide treatment.

Although most HER2-enriched tumors are HER2-positive (and named for this reason), many are HER2-negative [48].

HER2-enriched tumors tend to be [46,48-49]:

• ER-negative
• PR-negative
• Lymph node-positive
• Poorer tumor grade

About 10-15 percent of breast cancers are HER2-enriched subtype [46-48].

Women with HER2-enriched tumors may be diagnosed at a younger age than those with luminal A and luminal B tumors [49,51].

HER2-enriched breast cancers that are HER2-positive can be treated with HER2-targeted therapies such as trastuzumab (Herceptin).

Race/ethnicity and molecular subtypes of breast cancer

Prevalence

Prevalence rates show the proportion of people who have a breast cancer (or other health condition) at a given point in time. Prevalence rates of some molecular subtypes of breast cancer differ by race.

Triple negative/basal-like tumors appear to be more common among non-Hispanic Black and African American women (especially before menopause) compared to women of other ethnicities [51-56].

Triple negative tumors may be more common among Hispanic women compared to non-Hispanic white women [54,57-58].

Luminal A tumors may be more common among white women compared to women of other ethnicities [55,62].

Although the reasons for these differences are not clear, some lifestyle factors may play a role [58,62].

Learn more about race/ethnicity and breast cancer.

Learn more about race/ethnicity and risk factors for triple negative breast cancer.

Prognosis (chance of survival)

Higher rates of triple negative/basal-like tumors may explain, to some degree, the poor prognosis of breast cancers diagnosed in Black, non-Hispanic Black and African American women [54,63-65].

Also, luminal A tumors, which have the best prognosis of the molecular subtypes, occur less often in Black women than in white women [55,62].