Do You Still Need Chemo for Breast Cancer?

Breast cancer is highly treatable, and the majority of patients who receive proper care live long, healthy lives. But the diagnosis can still spark a great deal of anxiety. A person’s first instinct may be to think that aggressive treatment is the best way to go, but evidence suggests that is not necessarily the case.

Cancer treatments have changed—to the point where women with certain types of breast cancers need less treatment than they might have anticipated. While some form of surgery—either a mastectomy or lumpectomy—will usually still be necessary, chemotherapy, a range of drugs that can eradicate cancer cells but cause harsh side effects, might be minimized or not used at all for some patients. In fact, some patients may ultimately do better on other therapies.

“The more targeted treatments get, the more potential there is to tailor treatment for the individual,” says oncologist Eric Winer, MD, director of the Yale Cancer Center and physician-in-chief of the Smilow Cancer Network, who has focused his research on chemotherapy and biology’s role in personalizing its delivery. “And that's exactly what has happened with breast cancer. We now have clinical trial results showing that many women don't need to do all of this very toxic therapy,” he says.

If you or a loved one has been diagnosed with breast cancer, there is a lot to understand about the latest approaches to chemotherapy use.

Dr. Winer and Maryam Lustberg, MD, MPH, director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, answered some common questions about advances in breast cancer treatment.

Years ago, people thought about breast cancer as a single, monolithic, often life-threatening disease. The disease was subdivided into four stages: In Stage I, the tumor is small and has not spread beyond the original site; with Stage II and III cancers, the tumor is larger than in Stage I and may have spread to the lymph nodes; and in Stage IV, cancer has spread, or metastasized, to other parts of the body.

Outside of their stages, these cancers were thought to be the same disease, and every patient was given the same treatment.

“But stage is really just the amount of cancer,” Dr. Winer says. And while the stage is still part of determining treatment, it’s more important to take into account the type of cancer, he adds.

To that end, the types of breast cancers are categorized by their hormone receptors (estrogen and progesterone) and what’s called “HER2” status.

Breast cancer cells that contain receptors for hormones like estrogen and/or progesterone (which can help the cancer cells grow) are said to be hormone receptor (HR)-positive. And cancer cells that have high levels of receptors are called human epidermal growth factor receptor 2 (HER2)-positive. (HER2 is a protein that helps HER2-positive cancer cells grow.)

Cancer cells that do not contain hormones or HER2 receptors are called hormone receptor (HR)-negative or HER2-negative, respectively.

And breast cancers that do not have receptors for estrogen, progesterone, and HER2 are known as triple-negative.

With this in mind, doctors now know that identifying the correct subtype of breast cancer helps in personalizing treatment to that specific cancer, which means a one-size-fits-all approach no longer applies.

“Even the smallest breast cancers, depending on their biology—or type—may need targeted therapies that can help reduce the risk of a recurrence,” says Dr. Lustberg. “Through advances in clinical trials, breast cancer specialists are now better able to select therapies that are beneficial for different subtypes of breast cancer, leading to better individual and overall outcomes.” 

Chemotherapy can shrink cancer and slow its growth, which is why it has been used to treat breast cancer in conjunction with surgery for so many years. But the side effects can be difficult.

In the short term, these side effects can include such problems as nausea, fatigue, and hair loss, which can sometimes last far beyond treatment. “We know that, after a course of chemotherapy, a number of women, up to several years out, don't regain their full vitality,” Dr. Winer says. 

But even more concerning are the long-term effects, which can include rare, but difficult, complications such as heart problems, neuropathy, and leukemia, which can ultimately—and indirectly—affect outcomes.

These potentially debilitating side effects are why personalizing chemotherapy treatment has become so important. ”If a patient can do just as well with fewer medical treatments, it's almost always a better thing,” says Dr. Winer. Less chemotherapy can mean fewer side effects, less anxiety, improved quality of life, and possibly even a longer life, he adds.

Also, when side effects are truly debilitating, treatment delivery may be impaired, Dr. Lustberg says. “If we can enhance how patients are feeling during treatment, they may actually tolerate treatment better, stay on it longer, not need dose reductions or modifications, and have better disease outcomes. It's all interrelated.”

Research in the last two decades has shown that two types of breast cancer respond well to less-intensive chemotherapy—or none at all—in some cases:

• HR-positive: This is the largest breast cancer subtype, accounting for as many as 75% of all cases. The majority of women diagnosed with this subtype of breast cancer have no lymph node cancer at the time of diagnosis. Both for these women and many with positive lymph nodes, hormonal therapy is the most important treatment, and chemotherapy may not be needed, Dr. Winer says.
• HER2-positive. This aggressive breast cancer makes up 15 to 20% of breast cancer cases. Once a deadly disease, even in its early stages, it is now curable in more than 90% of cases, Dr. Winer explains. “In early [stage] HER2-positive cancers, we’ve found that very limited courses of chemotherapy can be just as effective as treatment that is more extreme,” he says.

Early in the 2000s, trastuzumab (Herceptin), a monoclonal antibody, was introduced to treat women with relatively advanced cases of HER2-positive breast cancer, and it was successful, Dr. Winer explains.

“Suddenly, women with relatively advanced forms of breast cancer—with lymph node involvement—were doing exceptionally well,” he says. “So, then we asked ourselves: ‘If you have a very small HER2-positive breast cancer and no lymph node involvement, do you still need such complex chemotherapy treatments?’ In a study published in the New England Journal of Medicine almost a decade ago, we demonstrated that one could give a limited course of chemotherapy along with trastuzumab and achieve outstanding results.”

Almost all women with HER2-positive cancers still need some amount of chemotherapy. And women with triple-negative tumors still need a relatively intensive course of chemotherapy, Dr. Lustberg says.

Chemotherapy may also be used to treat certain larger HR-positive cancers that have spread to lymph nodes, even if the tumor is estrogen-positive. "Specialized testing can determine which of these breast cancers will benefit from chemotherapy," Dr. Lustberg says. “Because of the personalized therapy made possible by these predictive biomarkers, the use of chemotherapy in lymph node-negative and lymph node-positive HR-positive cancers has decreased in recent years, with excellent clinical outcomes.”

Genomic profiling tests can help determine if a cancer is likely to return and whether or not some patients with small, early cancers will or will not benefit from chemotherapy.

“There are many of these tests, and the two most common ones are Oncotype DX and MammaPrint,” Dr. Lustberg says, adding that both are FDA-approved. The tests analyze a sample of a cancer tumor—taken from a biopsy or a surgical specimen—looking for the activity of certain genes that can affect the likelihood that a patient’s cancer will grow or spread.

The following patients may be eligible for the Oncotype DX test:

• You’ve recently been diagnosed with Stage I, Stage II, or Stage IIIa invasive breast cancer
• The cancer is estrogen-receptor-positive
• The cancer is HER2-negative
• The cancer is lymph node-positive or lymph node-negative

The MammaPrint can only be used to analyze early-stage breast cancers; it can be used on cancers that are:

• Stage I or II
• Invasive
• Smaller than 5 centimeters
• In three or fewer lymph nodes
• Hormone-receptor-positive and hormone-receptor-negative

The results of each test show an estimate of the patient’s risk for breast cancer recurrence over the next 10 years and a determination of what benefit chemotherapy may provide to help the clinician and the patient make treatment decisions.

The amount of chemotherapy, if it's needed, is typically based on such factors as the tumor subtype and other medical issues the patient may have, such as a cardiac condition.

“We want to be smart about chemotherapy,” Dr. Lustberg says. “Multiple studies have shown that if there is an opportunity to use other, smarter, and more targeted drugs, the patient’s quality of life can be actually better, and they may have a better outcome.”

For example, targeted therapies and anti-estrogen therapies are other treatment methods that are also excellent systemic therapy options and can lower the risk of cancer recurrence, depending on the particular form of breast cancer, Dr. Lustberg adds.  

It may help to know that there is solid research behind minimizing chemotherapy for some patients, says Dr. Winer. And that means that providers have already begun to implement this strategy.

Breast surgeons and radiation oncologists have learned that less treatment is the best approach for many patients. Breast surgeons, who were the first to take this approach, are not only doing lumpectomies instead of mastectomies, they are also doing fewer lymph node surgeries, lowering the risk for such problems as lymphedema and other challenges that can arise after breast surgery, Dr. Winer says. Therapeutic radiologists also are delivering treatments in shorter, more tolerable doses.

Of course, some patients, depending on their diagnosis, will still need more aggressive treatment, including chemotherapy.

And then there are situations where there could be a very small benefit from having chemotherapy. That benefit might be anywhere from zero—truly zero—to 2%, Dr. Winer explains. 

“Sometimes, a patient in that situation will take the treatment—and that decision is a very personal one. Our role as oncologists is to guide patients and help them make the best decisions,” he says, acknowledging that for some people, the most intensive treatment may feel like the best approach, even if the benefits are small.