Lincon

Although still in the early stages of research, 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 [35-36].
Other less common molecular subtypeshave 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 only in research settings and are not a part of standard medical practice. Prognosis and treatment decisions are guided by tumor stage,hormone receptor statusand 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 characteristicsthat are already well understood.
Figure 4.9
Subtype These tumors tend to be* Prevalence
Luminal A ER+ and/or PR+, HER2-, low Ki67 42-59%
Luminal B ER+ and/or PR+, HER2+ (or HER2- with high Ki67) 6-19%
Triple negative/basal-like ER-, PR-, HER2-, cytokeratin 5/6 + and/or HER1+ 14-20%
HER2+ ER-, PR-, HER2+ 7-12%
*These are the most common profiles for each subtype. However, not alltumors within each subtype will have all these features.
Adapted from selected sources [27,37-44].

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 like the cells of breast cancers that start in the inner (luminal) cells lining themammary 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 15 percent of luminal A tumors have p53 mutations, a factor linked with a poorer prognosis [27].
Of the four subtypes, luminal A tumors tend to have the best prognosis, with fairly high survival rates andfairly low recurrence rates [27,45-47].
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+)
• Lymph node-positive
Women with luminal B tumors are often diagnosed at a younger age than those with luminal A tumors [43,47]. And, compared to luminal A tumors, they also tend to have factors that lead to a poorer prognosis including [27,43,45,47]:
• Poorer tumor grade
• Larger tumor size
• p53 gene mutations
In general, women with luminal B tumors have fairly high survivalrates, although not as high as those with luminal A tumors [27].
Triple negative/basal-like
Triple Negative Breast Cancer
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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 many contain p53 mutations [27,45-46].
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 14 to 20 percent of breast cancers are...