Phyllis Lacetti found her own breast cancer when she felt an abnormal lump in her right breast in 2007. A nurse at Montefiore Medical Center, she had a lumpectomy to remove it, but an MRI afterward revealed remaining cancer cells, so she opted to get a mastectomy.
Her cancer doctor recommended she get chemotherapy to ensure that her cancer wouldn’t recur, since Lacetti’s family history put her at high risk. Her sister and father had died of leukemia, and her brother passed away from thyroid cancer. Chemotherapy, he said, was her best option for preventing the cancer from returning.
But Lacetti was reticent about getting the toxic therapy. “I saw my sister suffer, I saw my brother suffer, and I didn’t know if that’s what I wanted to do,” she says.
Her doctor, Dr. Joseph Sparano, associate director of clinical research at Albert Einstein Cancer Center at Montefiore, happened to be heading up a large study investigating whether women like Lacetti could safely avoid getting chemotherapy. He was comparing women who had been treated with surgery or radiation who were then only given hormonal therapies (that block hormones like estrogen, which fuel tumor growth), to women who received both hormone therapies and chemotherapy. Lacetti was eager to join to help doctors learn more about whether chemo was really necessary for people like her.
Nearly 10 years later, Lacetti knows she made the right decision. She was randomly assigned, as she had hoped, to the hormonal therapy group, so she never received chemotherapy. She and the more than 10,000 other women from around the country who participated in the trial showed that for most women with early-stage breast cancer, chemotherapy does not provide any additional benefit in reducing recurrence, or from dying of the disease.
“I feel relief that, wow, now there is proof out there that there’s no difference if you don’t do chemo,” she says.
Those results apply to the majority of women diagnosed with breast cancer in the U.S., and could dramatically change their treatments. The majority of the more than 260,000 new cases of breast cancer diagnosed in the U.S. each year are picked up at the early stages, as Lacetti’s was, and half have not yet spread to the lymph nodes. About 80% of them are dependent on the hormone estrogen, so anti-estrogen treatments are generally effective in keeping them under control.
For these women, Sparano’s trial, called TAILORx, is a game changer. Since 2000, the National Institutes of Health has recommended that women treated for early-stage breast cancer with surgery or radiation also receive chemotherapy as a safety net — primarily based on data from more advanced cases of breast cancer that showed that chemo could ensure that any rogue cells missed by the other treatments don’t escape to grow again. Even after anti-estrogen treatments, known as aromatase inhibitors, were introduced as part of the regimen in recent decades, they were simply added on to chemotherapy.
The benefits, doctors believed, justified the often toxic side effects that come with the powerful drugs. Many women experience nausea, vomiting, severe fatigue and sleep disruptions during chemotherapy, although some of the newer options come with fewer adverse effects. Some studies also point to potential long-term health problems linked to chemotherapy, including certain additional cancers.
In a recent presentation at the annual meeting of the American Society of Clinical Oncology and in a study published in the New England Journal of Medicine, researchers now report that chemotherapy may be unnecessary for many women with early-stage cancers. Their findings show that hormonal therapies, which women typically take for five years, are enough. Both the women taking hormone treatment alone and those taking the combination of hormone treatment and chemotherapy had a nearly 94% chance of surviving their cancer after nine years. “The important take-home message is that we have an unprecedented level of evidence with which to make treatment recommendations with an unprecedented level of precision,“ says Sparano.
These findings apply mostly to older women who are past menopause. For younger women with intermediate risk scores, there may be some benefit to chemotherapy in lowering their risk of recurrence. While it’s not clear why, it’s possible that they are still exposed to more estrogen than older women, since estrogen levels drop after menopause.
But the results provide much-needed reassurance to doctors and patients who have been questioning how much treatment is enough in recent years. “We’ve always known that we are over-treating with chemotherapy,” says Dr. Sara Hurvitz, director of the breast oncology program at University of California Los Angeles.
That realization began in 2015, when the first arm of TAILORx revealed that a genetic test could identify women at low risk of recurrence who did not need chemotherapy. Oncotype DX, which predicts likelihood of recurrence on a scale from 0 to 100, analyzes 21 genes that are important in cancer growth; a low score indicates a low risk of the cancer coming back, and therefore less need for chemotherapy, while a high score indicates a higher chance of recurrence, and a more urgent need for chemotherapy.
But for women whose scores fell in the middle, between 11 and 25 and defined as intermediate risk, the decision about chemotherapy was less clear. “I would spend a lot of time with my patients saying we don’t know what the absolute benefit of chemotherapy is for you,” says Dr. Dawn Hershman, director of the breast cancer program at New York Presbyterian Columbia University Medical Center. Most doctors ended up erring on the side of caution. “I have been leaning toward chemo,” says Dr. Larry Norton, medical director of the Evelyn Lauder Breast Center at Memorial Sloan Kettering Cancer Center. “Everything else being equal, it’s better to treat and prevent metastasis than not to treat and allow metastasis.”
This better-safe-than-sorry approach has led to unnecessary treatment. While the first arm of TAILORx showed that women with scores below 10 might not need chemotherapy, now the latest findings add more than 60,000 women in the U.S. to that group. The results provide the same level of confidence for those with scores from 11-25 that chemo does not appear to lower their risk of recurrence significantly compared to women taking hormonal therapies alone. “Chemo is not killing any more cancer cells than are being killed by hormone therapy,” says Norton. “I don’t see chemo playing a role in this setting at all.”
The results may herald a new era in which doctors make smarter decisions about how much is enough when treating different cancers. “This is the dawn of the de-escalation era,” says Hurvitz. “We need to move forward looking for ways to de-escalate therapy that is not just limiting quality of life, but also potentially harming patients.”
That streamlining can also contribute to cost savings. The Oncotype DX test runs about $3,000-$4,000 (most insurers cover it) but for tens of thousands of women, it could potentially spare them from chemotherapy, which can cost on average $20,000.
Even apart from the financial benefit, for women like Lacetti, the findings provide welcome reassurance that they can avoid a dreaded part of cancer care that comes with serious side effects and long-term health consequences. “It’s wonderful,” she says. “My sister had to quit her job to do chemo, and stayed in the hospital for 11 months. I’m able to keep my job, and spend more time with my family. I’m glad they had this study, and I’m glad I was able to be a part of it.”