November 2016 Ask the Expert: Know Your Subtype

November 1, 2016

Breast cancer is often thought about as one disease. But in reality, different breast cancers grow for different reasons and need different treatments. There are three main subtypes of breast cancer: hormone receptor-positive, HER2-positive and triple-negative. Do you know your subtype?

Researchers have created therapies specific to certain subtypes to best treat each type of the disease. They’re always learning more about these subtypes, trying to find new subtypes, and working to create new treatments.

In November, Living Beyond Breast Cancer expert Debu Tripathy, MD answered your questions about breast cancer subtypes.

Remember: we cannot provide diagnoses, medical consultations or specific treatment recommendations. This service is designed for educational and informational purposes only. The information is general in nature. For specific healthcare questions or concerns, consult your healthcare provider because treatment varies with individual circumstances. The content is not intended in any way to substitute for professional counseling or medical advice. 

This Ask the Expert residency was sponsored by AstraZeneca.

How do rates of recurrence change based on what kind of breast cancer you have?

There are several factors that influence the risk of recurrenceinfo-icon. The stageinfo-icon of the cancer, including the tumorinfo-icon size and whether and how many of the lymphinfo-icon nodes under the arm are affected, is important. The gradeinfo-icon of the tumor also influences the risk of recurrence. HER2-positive and triple-negative breast cancers are associated with a higher risk of recurrence, although with the availability of HER2-targeted therapies, HER2-positive cancers aren’t considered as a high risk as they used to be.

There are newer tests, called geneinfo-icon profiles, that examine multiple genes at a time and can help categorize breast cancer risk more accurately. In certain breast cancer cases, this can help when making decisions about the need for chemotherapyinfo-icon.

Are researchers close to finding more breast cancer subtypes and learning how to treat them?

Many advances in technology help find and measure mutations in several genes, which allows doctors to classify some breast cancers above and beyond the classical biomarkers of estrogeninfo-icon, progesteroneinfo-icon and HER2 receptors. But the primary decisions are still made on the basis of these three receptors. Some decision-making though, especially about whether to add chemotherapyinfo-icon to hormonal therapyinfo-icon for people with hormone receptorinfo-icon-positive, HER2-negative breast cancer, is being made with commercially available geneinfo-icon profiling tests. Mutations are increasingly being used to match people to specific clinicalinfo-icon trials, but research hasn’t yet shown this should be standard.

Are certain subtypes more likely to respond to certain lifestyle changes, like quitting smoking, losing weight, etc.?

There is very little information about whether lifestyle changes affect how certain subtypes respond to treatment or how likely they are to recur. There is some evidence to suggest that obesity, particularly in postmenopausal women, raises the risk of hormone receptor-positive breast cancer. But doctors generally recommend that people with any subtype of breast cancer live a healthy lifestyle that includes maintaining an ideal body weight, exercising regularly, drinking alcohol in moderation or not at all, and avoiding tobacco.

I know breast cancer can run in families, but can certain subtypes run in families too? Are my relatives more likely to get triple-negative breast cancer because I have triple-negative breast cancer?

Yes, there are associations between certain subtypes and some hereditaryinfo-icon breast cancers. For example, in people who carry a mutationinfo-icon in the BRCA1info-icon geneinfo-icon, 80 to 90 percent of breast cancers that develop are triple-negative. But in BRCA2info-icon mutation carriers the different subtypes are distributed the same as in the general population. Due to the association of BRCA1 mutations with triple-negative breast cancerinfo-icon, it is now recommended that anyone with triple-negative breast cancer under the age of 60, regardless of family history, be referred for genetic counselinginfo-icon and testing.

Can I still take birth control pills if I am diagnosed with hormone receptor-positive breast cancer?

There is very little known about the impact of birth control pills when used to prevent pregnancy in people who are diagnosed with hormone receptorinfo-icon-positive breast cancer. Because there is an association between estrogeninfo-icon and progesteroneinfo-icon and the development of breast cancer, doctors generally advise women with a history of breast cancer to use non-oralinfo-icon or non-progesterone contraceptive methods, such as an intrauterine device (IUD).

Did my race or age make me more likely to be diagnosed with a certain subtype?

There are certain subtypes of breast cancer that are more common in specific racial or age groups. For example, triple-negative breast cancerinfo-icon (negative for estrogeninfo-icon, progesteroneinfo-icon and HER2 receptors) is more common in people of African or African-American descent for reasons not fully understood. It is also more frequent in younger people, in part because BRCA mutationinfo-icon-related breast cancers tend to appear at a younger age, and breast cancers associated with BRCA1info-icon mutation are much more likely to be triple-negative.

On the other hand, breast cancers that appear in post-menopausal women are more likely to be hormone receptorinfo-icon-positive and less aggressiveinfo-icon. In fact, post-menopausal women have a lower chance of dying of breast cancer compared to those diagnosed at a younger age.  

People I’ve talked to who also had hormone receptor-positive breast cancer took hormonal therapy for about 5 years, but my doctor is saying I’ll have to take it for 10. Is that right? Why would that be?

Hormoneinfo-icon-responsive breast cancers (those positive for estrogeninfo-icon receptors, progesteroneinfo-icon receptors, or both) can recur or metastasizeinfo-icon years and even decades after the initial diagnosisinfo-icon. For that reason, it was assumed that hormonal therapyinfo-icon should be given for several years. When the first medical hormonal therapy (it really should be termed “anti-hormonal” therapyinfo-icon), tamoxifeninfo-icon, was tested, studies compared taking the medicineinfo-icon for 1 versus 2 years, and then 2 versus 5 years. These studies found 5 years of treatment to be most effective in lowering the risk of recurrenceinfo-icon.

But since recurrence still can occur even after that point, studies comparing 5 versus 10 years of treatment were started. These results have become available in recent years and do show a few percentage point reductions in recurrence with 10 compared to 5 years of tamoxifen or with the aromatase inhibitorinfo-icon letrozoleinfo-icon (Femarainfo-icon). The differences are modest, and must be balanced against long-term side effects. In those at higher risk for recurrence, such as those with positive lymphinfo-icon nodes, we assume the differences are larger and may provide more motivation to recommend 10 years of hormonal therapy.

I’ve heard there’s another subtype called androgen receptor-positive. What is that?

Yes, the androgen receptorinfo-icon (AR) is present in several tissues in both men and women, and is also expressed in some breast cancers. This is the case more often in hormone receptorinfo-icon-positive cases, but it’s also seen in cases that are otherwise considered triple-negative. The big question is whether blocking AR can treat breast cancer, as is the case with prostate cancers which almost always express AR. AR-blocking medicines like bicalutamide (Casodex) and enzalutamide (Xtandi) have been tested in breast cancer and responses have been seen in a small percentage of AR-positive cases. These trials are small pilot studies, and efforts are underway to do large-scale testing and also to combine AR blockers with standard breast cancer medicines.

In metastatic breast cancer, do people with certain subtypes tend to survive longer than people with others?

Different metastaticinfo-icon breast cancer cases can take very different courses. One of the important variables that predict (although not fully) how long people may respond to different therapies and how long they may live is the presence of hormoneinfo-icon (estrogeninfo-icon and progesteroneinfo-icon) receptors (HR) and HER2 receptors. HR-positive metastatic cases tend to respond for longer periods of time (although not forever) to therapyinfo-icon, and less toxicinfo-icon hormonal therapies are usually tried first. HER2-positive breast cancer used to be very aggressiveinfo-icon with shorter life spans, but that has changed with the advent of several HER2-targeted medicines. Now people with this subtype can usually experience longer remissions. Triple-negative breast cancers only respond to chemotherapyinfo-icon and tend to have shorter responses (although some can have durable, long responses), so in general this subtype is considered the most aggressive. Much research is focused on defining new “targets” against which effective biological medicines can be developed.

Is triple-positive breast cancer considered a separate subtype? How common is it, and are any treatments used specifically for it?

Yes, breast cancer that is both HER2-positive and hormone receptorinfo-icon-positive is a distinct subset. With some of the newer classifications based on the expression levels of several genes, this subset is sometimes referred to as Luminal B. This subset of breast cancer is treated with both HER2-targeting medicines and hormonal therapyinfo-icon.

For early-stageinfo-icon disease, the treatment is typically chemotherapyinfo-icon with trastuzumabinfo-icon (Herceptininfo-icon) and sometimes pertuzumabinfo-icon (Perjeta). Both of those medicines are anti-HER2 antibodies. When the chemotherapy portion is completed, the anti-HER2 treatment is continued for a total time of 1 year. Hormonal therapy is also started when chemotherapy is completed and typically continued for 5 to 10 years.

For advanced breast cancer, chemotherapy and anti-HER2 medicines are also used. After a response is seen, the chemotherapy part is discontinued and replaced with hormonal therapy, but the anti-HER2 medicines are continued.

I know there’s been a lot of talk about extending the amount of time people take hormonal therapy. What about therapies for HER2-positive breast cancer? Could taking them longer lower the risk that the breast cancer will return?

There has been one large clinical trialinfo-icon that tested trastuzumabinfo-icon (Herceptininfo-icon) for a longer time period than the usual 1 year. This trial compared 1 year to 2 years of treatment and found no difference. But the low risk of heart problems was increased when people took the medicineinfo-icon longer. So the standard total treatment time with trastuzumab remains 1 year.

What should I know about the possibility that the breast cancer subtype will change after disease progression?

The breast cancer subtype can change from the primary cancer to the time of metastasisinfo-icon. It can change in either direction, from being positive for hormoneinfo-icon receptors or too many HER2 proteins to being negative, or from being negative to being hormone receptorinfo-icon-positive or HER2-positive. In about 5 to 10 percent of cases, breast cancer that was once called estrogen receptor-positiveinfo-icon is deemed estrogen receptor-negativeinfo-icon after a metastaticinfo-icon recurrenceinfo-icon. HER2 status can also change about 5 to 10 percent of the time.

It is difficult to know if the there was a difference in how the test was run or if the biology really changed. But our treatment recommendations are guided by the markers seen on the metastasis. So when possible, it is recommended a biopsyinfo-icon be done when a metastasis is seen, not only to confirm that it is truly a recurrence of cancer, but to determine estrogeninfo-icon, progesteroneinfo-icon and HER2 receptorinfo-icon status for treatment decisions.