Doctors are at odds over whether some women with breast cancer should have chemotherapy — one treatment among the arsenal long seen as crucial to fighting the disease, along with surgery and radiation.
Many oncologists are shunning chemo as risky and ineffective at combating some early-stage breast tumours. Traditionally, the majority of women with invasive breast cancer were treated with some combination of surgery, radiation and chemotherapy.
A shift to less chemotherapy or none at all, called “de-escalation”, is being hailed by some as revolutionary, following what these doctors see as years of over-treatment with drugs that may have harmed more than helped. Proponents of de-escalation say chemotherapy — the use of chemical agents to treat the disease — should be used only when it appears likely to reduce the chances of the cancer spreading.
De-escalation has exposed a rift among oncologists, with some worrying that women may not get the treatment they need to survive. Cancer mortality rates have improved since the late 1980s and some researchers credit chemotherapy for playing a role. In use since the 1940s, chemotherapy has become generally less toxic and more effective since the early days of nitrogen mustard. While it has side-effects such as nausea, doctors are more skilled at controlling them.
The fault lines over chemotherapy are emerging amid a larger debate about over-treatment. Concerns include whether too many antibiotics are being prescribed for ailments that don’t warrant them and whether surgery has been foisted on prostate cancer patients despite tumours that posed little risk.
Some doctors say the time has come to reassess treatment for breast cancer patients, too.
“Tens of thousands of women were over-treated, they got surgery they didn’t need, they got radiation they didn’t need, and they got chemotherapy they didn’t need,” says Steven Katz, a professor of medicine at the University of Michigan and a supporter of de-escalation, an approach that extends beyond chemotherapy to other treatments and other maladies. Chemotherapy, he says, “knocks the hell out of people and oncologists have gotten more sensitive to the harm” it can cause.
In the past, chemotherapy was widely considered crucial to care. But advances in understanding tumour biology have changed the way many doctors approach chemotherapy. With genomic testing — which looks at genes that affect cancer — a tumour is given a score. A low score means a woman has a good prognosis and won’t benefit from chemotherapy. A higher score suggests a greater risk of recurrence and a need for conservative chemotherapy treatment. The middle scores — which are fuelling physicians’ angst — are in a grey zone in terms of data on whether to prescribe chemotherapy.
In 2014 Faye Ruopp, of Chestnut Hill, Massachusetts, learned she had invasive breast cancer. Her tumour was 1.3cm and “growing fast”, says Ruopp, a former maths teacher. On the genomics test, her tumour got an ambiguous score — “at the top of the low end”.
Ruopp’s physician, Eric Winer, director of the Breast Cancer Program at Dana-Farber Cancer Institute in Boston, says her case wasn’t a “slam dunk”. Indeed, Winer says: “There was the very real possibility we would give her chemotherapy.”
Patient and doctor discussed the pros and cons and decided against chemotherapy. Her treatment consisted of the original lumpectomy surgery, radiation and hormonal therapy. Ruopp, now 67 and a maths coach, had hoped to avoid chemo and she has no misgivings. “You need to trust your oncologist,” she says.
Treatments for those who decide against chemotherapy still include surgery and radiation. Women whose tumours are deemed receptive to the hormone oestrogen will get hormone therapy. They can take pills, such as Tamoxifen, which reduces the risk of recurrence.
Use of chemotherapy to treat early breast cancer has been declining, according to a study led by Katz and Stanford oncologist Allison Kurian published in December in the Journal of the National Cancer Institute. The study of about 3000 women with early-stage breast cancer — and about 500 doctors who treated them from 2013 to 2015 — found that use of chemotherapy declined overall during that time, to 21.3 per cent of cases from 34.5 per cent.
In an accompanying editorial, the senior author, Dana-Farber’s Dr Winer, highlighted chemotherapy’s drawbacks. While chemo can have “limited” benefits, he wrote, “toxicity can be formidable” and long-term effects can include leukaemia, heart failure, neuropathy, premature menopause and infertility.
Winer says he is “not afraid of chemotherapy”, which he prescribes when necessary. The challenge is balancing risks and benefits, he says; for some patients, the risks are substantial but there is little or no benefit.
“The medical community has underestimated the side-effects and impact on a woman’s life,” Winer says, adding that thanks to strides in understanding breast cancer, “we may be able to do less without compromising outcomes”.
Among the chemotherapy drugs commonly used against breast cancer are many that are administered intravenously. As well as nausea, side-effects can include hair loss and fatigue.
The de-escalation debate, Winer says, isn’t about these drugs, which oncologists generally agree can be effective in certain cases. Rather, the debate is about which patients and their cancers would benefit from such regimens.
Other doctors at major cancer centres worry that a less aggressive approach poses dangers. The attacks on chemotherapy are scaring patients, they say, and could prevent them from making life-saving decisions. Meanwhile, data on the effect of withholding chemo from more complex breast cancers is still lacking, they argue.
At the Memorial Sloan Kettering cancer centre in New York, physician-in-chief Jose Baselga says that while there is data to support forgoing chemotherapy on certain women with early-stage disease, these are “a fraction” of cases. In some cases withholding chemo carries big risks, he warns. “People will die because they will not get the therapy they need.” One of Baselga’s patients, Evette Fairweather, was diagnosed with early-stage invasive breast cancer in 2013. Her 1.5cm tumour had a genomics test score of 19, placing her in the ambiguous zone of whether to have chemotherapy. After Baselga said it would reduce her risk of recurrence, Fairweather, who is now 51, decided to overcome her fears of the treatment and proceed with it.
While receiving chemo drugs over several months, Fairweather, a payroll processor, kept working. “I won’t say I felt great, but I was able to bounce back,” she says. “I didn’t throw up. I ate a lot.” Now relocated to Atlanta, she comes to New York twice a year to see Baselga and feels fine. She has no regrets about her decision.
Baselga worries that there is a “pack behaviour” in the breast-cancer community that could lead doctors to embrace doing less before such an approach has proved itself through rigorous studies. For more complex cases, “we need to make clinical decisions based on data, not on beliefs or wishes”, he says.
De-escalation advocates “have these buzzwords they use quite lightly such as chemotherapy being a poison. Are you kidding me?” he says. “Chemotherapy has saved many, many lives. There is zero question about that.”
The breast cancer field, Baselga says, is littered with once-vaunted treatments that later research proved to be failures. In the 1990s patients were given bone marrow transplants and high-intensity chemotherapy — a costly, agonising treatment that didn’t work. Now the pack is headed in another direction, he says. “One day we are going to transplant everyone and the next we are not going to do chemo.”
A paper published in the New England Journal of Medicine in 2015 gave de-escalation supporters powerful ammunition. In a study of more than 10,000 women, 1626 who had early-stage breast cancer with no lymph node involvement were given hormonal treatment alone, without chemotherapy. The study, led by Joseph Sparano, an oncologist and professor of medicine at Albert Einstein College of Medicine in New York, found that those with a low score also had “very low rates of recurrence at five years with endocrine therapy alone”. In other words, they did fine without chemotherapy.
Oncologists are awaiting the results from the next phase of his research. Sparano, an oncologist at New York’s Montefiore Health System, will focus on more ambiguous and complex breast cancer cases with mid-range scores.
The conundrum lies with these “close calls”, says Stanford’s Kurian. Will de-escalation lead to errors? “I would hate for doctors and patients to say chemotherapy was oversold,” she says. “Some patients don’t need it, but a subset does need it to reduce their chance of death.”
According to Otis Brawley, chief medical and scientific officer of the American Cancer Society, in the late 1980s the mortality rate for breast cancer was 32.2 deaths per 100,000 women; by 2015 the death rate was 20.5 deaths, or a 39 per cent decrease. Brawley backs de-escalation, saying that with genomics testing, “we are hopefully identifying the women that need the chemotherapy and more importantly the women who don’t need the chemotherapy”.
At the MD Anderson Cancer Centre in Houston, oncologist Gabriel Hortobagyi, in practice for more than four decades, can still recall the years when high percentages of women died from breast cancer. He credits chemotherapy for helping achieve a turnaround, saying “tens of thousands, maybe hundreds of thousands” owe their lives to it.
Genomic tests can help determine who can benefit from chemotherapy, says Hortobagyi, but he worries about “pejorative” attacks on chemo.
“There is clearly a need for addressing the toxicities of the treatments,” Hortobagyi says, “but we have to do it responsibly and on the basis of the highest level of evidence. We can’t simply go out and say, ‘As of tomorrow, I will go and give half the chemo’, in the absence of evidence that [it] would work.”
Besides, he adds, “the worst toxicity is death”.
