Subtypes of Breast Cancer

Although still in the early stage of research, molecular breast cancer subtypes may become useful in planning treatment and developing new therapies. One theory divides breast cancer into four molecular subtypes: luminal A, luminal B, triple negative/basal-like and HER2/neu-positive. Breast cancers that do not fall into these four subtypes are often listed as unclassified or normal breast-like subtype. These same subtypes also appear in ductal carcinoma in situ  [47]. At this time, molecular subtypes are used only in research settings and are not a part of standard medical practice. Prognosis  and treatment decisions are 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. On a basic level, characteristics (including hormone receptor status and the presence of certain cellular proteins) can be used to loosely define the four subtypes (see Figure 4.9 below). Much of what is known about these subtypes is related to those characteristics that are already well understood, such as hormone receptor and HER2/neu status. 

Figure 4.9

Find out more on hormone receptor status (estrogen receptor status and progesterone receptor status). 

Find out more on HER2/neu status.  

Luminal A

Most breast cancers are luminal tumors, starting in the inner (luminal) cells that line the mammary ducts. Luminal A and luminal B tumors are both are most often estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+). However, luminal A tumors tend to be HER2/neu-negative (HER2-) and luminal B tumors tend to be HER2/neu-postive (HER2+). Only about 15 percent of luminal A tumors have p53 mutations, a factor linked with a poorer prognosis [21]. 

Of the four subtypes, luminal A tumors tend to have the best prognosis, with fairly high survival rates and fairly low recurrence rates [21,54-56].   

Luminal B

Luminal tumors start in the inner (luminal) cells that line the mammary ducts. Luminal B tumors are like luminal A tumors in that they tend to be estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+). They also tend to have a high Ki67 score (high proliferation rate, that is a high number of cancer cells actively dividing) [53]. However, unlike luminal A tumors, luminal B tumors tend to be HER2/neu-positive (HER2+) and lymph node-positive. They also tend to have poorer tumor grade, larger tumor size and poorer prognosis and are more likely to have p53 mutations [21,53,55]. Women with luminal B tumors are often diagnosed at a younger age than those with luminal A tumors [53,54].

In general, women with luminal B tumors have fairly high survival rates, although not as high as those with luminal A tumors [21].  

Triple negative/basal-like 

Triple Negative Breast Cancer PDF, 2.97M

A triple negative tumor is estrogen receptor-negative (ER-), progesterone receptor-negative (PR-) and HER2/neu-negative (HER2-) [57]. Basal-like tumors have cells with features similar to those of the outer (basal) cells that line the mammary ducts. Estimates on the prevalence of basal-like tumors vary from 13 to 28 percent [21,48-53]. Basal-like tumors are often linked to BRCA1 breast cancers and may occur more often in younger women [58]. There is so much overlap between these two subgroups of tumors that they are often listed as one subgroup. 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). 

These tumors also tend to express HER1 and/or cytokeratin 5/6- proteins and many contain p53 mutations [21,55,58]. Triple negative/basal-like tumors are often aggressive and have a poorer prognosis compared to the estrogen receptor-positive subtypes (luminal A and luminal B tumors) [21,49,51,56].  Most BRCA1 breast cancers and many BRCA2 breast cancers are both triple negative and basal-like [59].
Treatment choices for triple negative/basal-like tumors are limited because of their triple negative qualities. Most often these tumors cannot be treated with trastuzumab (Herceptin) or hormone therapies because they are HER2/neu-negative and hormone receptor-negative. Because the genes linked to basal-like tumors are not well understood, targeted therapies do not yet exist. However, potential targets for future therapies have been identified and include the EGF receptor, aB-crystallin and cyclin E [57]. Clinical trials studying treatment options for triple negative/basal-like tumors are underway. Learn more about clinical trials .

Find information on Susan G. Komen for the Cure’s® work with the Triple Negative Breast Cancer Foundation (TNBC). 

HER2/neu-positive (HER2+)

HER2+ tumors are named for their HER2/neu-positive status. They tend to be estrogen and progesterone receptor-negative (ER-/PR-), lymph node-positive tumors with poorer tumor grades [21,54,55,60]. About seven to twelve percent of breast cancers have this molecular profile. Many HER2+ tumors contain p53 mutations [21,60]. HER2+ tumors have fairly poor prognosis and are prone to early and frequent relapse and distant metastases [21,49,54-56]. Women with HER2+ tumors appear to be diagnosed at a younger age than those with other subtypes [49].

Unclassified/normal breast-like

Tumors that do not fit the profiles of the other four subtypes are often called unclassified or normal breast-like tumors. Although this category is called “normal breast-like”, it does not mean that these tumors are the most common (or most normal) type of breast cancer. About six to10 percent of all breast cancers fall into the unclassified/normal breast-like category [21,49]. These tumors are most often small and tend to have a good prognosis [21,55]. Normal breast-like tumors are more common among postmenopausal women than premenopausal women [55]. However, it should be noted that 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 contained a lot of normal (not cancer) tissue.

Race/ethnicity and subtypes of breast cancer

There appear to be racial differences among the prevalence rates of the four subtypes of breast cancer. 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 [21,45,52,61,62]. Although the reasons behind this relationship are not clear, one study suggested that lifestyle factors might play a role. African American women in the study tended to have lower rates of breastfeeding and to carry excess weight in the tummy area, both of which increased the chances of having triple negative/basal-like tumors [52]. 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 [21].

Updated 10/27/09

Emerging Areas in Diagnosis	References
Emerging Areas in Chemotherapy, Hormone Therapy and Targeted Therapy