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Molecular Subtypes of Breast Cancer

 

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:

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

These same subtypes also appear in ductal carcinoma in situ [38-39].  

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 

These tumors tend to be*  

Prevalence (approximate) 

Luminal A

ER+ and/or PR+, HER2-, low Ki67

40%

Luminal B

ER+ and/or PR+, HER2+ (or HER2- with high Ki67)

20%

Triple negative/basal-like

ER-, PR-, HER2-

15-20%

HER2 type

ER-, PR-, HER2+

10-15%

*These are the most common profiles for each subtype. However, not all tumors within each subtype will have all these features.

ER+ = estrogen receptor-positive

ER- = estrogen receptor-negative

PR+ = progesterone receptor-positive

PR- = progesterone receptor-negative

HER2+ = HER2/neu receptor-positive

HER2- = HER2/neu receptor-negative 

Adapted from selected sources [30,40-44].

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-)
  • Tumor grade 1 or 2

Fewer than 15 percent of luminal A tumors have p53 mutations, a factor linked with a poorer prognosis [30,45].  

Of the four subtypes, luminal A tumors tend to have the best prognosis, with fairly high survival rates and fairly low recurrence rates [30,43-44,46-47]. Because luminal A tumors tend to be ER+, 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:

  • ER+ and/or 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 [46,48]. And, compared to luminal A tumors, they tend to have factors that lead to a poorer prognosis including [30,43-46,48-49]:

  • 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 [30,44,46].
 

Triple negative/basal-like 

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Triple Negative Breast Cancer
Fact Sheet

  Meet Nicole Vazquez, a woman living with triple negative breast cancer.  

Triple negative breast cancers are:

  • ER-
  • PR-
  • HER2-

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 mutations [30,40,45].

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). 

 

Triple Negative-basal Like Tumors Venn Diagram 

 

 

About 15 to 20 percent of breast cancers are triple negative or basal-like [30,40-45]. These tumors tend to occur more often in younger women and African American women (more on race/ethnicity and subtypes of breast cancer) [30,44,48,50-54]. And, most BRCA1 breast cancers are both triple negative and basal-like [44,50,55-56].  

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) [30,40,43-44,57].  

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 ER- and HER2-.  

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 [58].  

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®'s work with the Triple Negative Breast Cancer Foundation (TNBC) and research we are funding to study triple negative breast cancer.

 Komen Perspectives 

Read our perspective on triple negative breast cancers (February 2012).* 

 

HER2 type

The molecular subtype HER2 type is not the same as HER2+ and is not used to guide treatment. Although most HER2 type tumors are HER2+ (and named for this reason), about 30 percent are HER2- [44]. HER2 type tumors tend to be [30,43-46,59]:

About 10 to 15 percent of breast cancers have this molecular profile [30,43-44]. About 75 percent of HER2 type tumors contain p53 mutations [30,45,59].  

HER2 type tumors have a fairly poor prognosis and are prone to early and frequent recurrence and metastases [30,43-44,51-52,60]. Women with HER2 type tumors appear to be diagnosed at a younger age than those with luminal A and luminal B tumors [42-43].  

HER2/neu-positive tumors can be treated with the drug trastuzumab (Herceptin). 
 

Normal-like

About six to 10 percent of all breast cancers are classified as normal-like [30,42]. Although called “normal-like,” these tumors are not more common than others. These tumors are usually small and tend to have a good prognosis [30].  

At this time, it is unclear whether normal-like tumors are a distinct molecular subtype [44]. 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 U.S. and British women, triple negative/basal-like tumors appear to be more common among black women (especially those who are premenopausal) compared to white women [30,44,52-54,61-63]. Although the reasons for this are not clear, some studies suggest lifestyle factors might play a role (learn more).  

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 [30].  

Luminal B and HER2 type tumors do not appear to differ by race [30].  

*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.   

Updated 02/05/14

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