For Women With Early Breast Cancer, Herceptin Treatment Can Be Much Shorter

During the past 20 years, hundreds of thousands of women with breast cancer have taken the drug Herceptin, typically for a year or more. The medicine, used to treat an aggressive form of the disease, is credited with saving many lives, but it also has some tough side effects, particularly damage to the heart.

A large new study that followed thousands of women with early-stage breast cancer for a median of more than five years has found that those treated with Herceptin for only six months did just as well as those who got it for a year — and they suffered fewer side effects.

The shorter regimen also saved money. A yearlong course of the drug costs $76,700.

Dr. Bruce E. Johnson, president of the American Society of Clinical Oncology, said the study’s findings should change treatment for women who have early-stage breast cancer treatable by Herceptin. He was not involved in the research, which was done in Britain and will be presented at a meeting of the oncology society next month.

“A lot of people will likely adopt a shorter regimen based on this finding,” Johnson said.

Cancer specialists say the study offers not only important news for women’s health, but also highlights a type of research that pharmaceutical companies rarely do and that is also critically important for cancer drugs that can often be quite toxic.

The study has not yet been published in a medical journal, and some experts reserved judgment until the data have been peer-reviewed. Johnson noted that as the field of cancer research matures, more efforts are being made to fine-tune treatments — lessening doses or duration, or even dropping some forms of therapy entirely for certain patients — to minimize harsh side effects without sacrificing efficacy.

For example, a study last year showed that many patients with colon cancer could safely shorten their course of chemotherapy from six months to three. And a study in 2016 found that many women with early-stage breast cancer, who traditionally would have been given chemo, could safely skip it, based on tests of gene activity in their tumors.

Dr. Otis W. Brawley, chief medical and scientific officer of the American Cancer Society, said there was also an increasing recognition among doctors that it is safe to monitor some early cancers, including certain tumors in the prostate, thyroid gland, kidney and bladder, rather than perform surgery immediately. Some tumors will eventually require removal, but others will not grow, spread or threaten the patient’s life or health.

The Herceptin study was paid for by the British government. Johnson said that although drug companies finance many studies, they are not eager to pay for research that may decrease use of their products.

Brawley agreed, saying: “When drug companies do research, they’re interested in gaining knowledge such that they can make money for their shareholders. There is a difference. You will not see drug companies doing this kind of study. They don’t mind that somebody else did it, but they will not get caught doing a study that decreases their bottom line.”

Courtney Aberbach, a spokeswoman for Herceptin’s maker, Genentech, owned by Roche, said in an email that previous studies had not found that a shorter duration worked as well as the longer one. She said the 12-month course was still the only regimen approved for early-stage disease by the Food and Drug Administration and recommended by several international organizations that issue treatment guidelines.

But Brawley pointed out that this type of research underlines the importance of government entities in conducting or supporting cancer research, because their goal is to increase understanding of the disease.

The new study is the first to show that women with early-stage disease can safely cut back on Herceptin, Dr. Helena Earl, its first author, at the University of Cambridge in Britain, said in an email.

“Here we are asking the question whether less is more,” she said.

Studies like the new one, aimed at finding out whether one treatment is no worse than another, are more difficult and more expensive — requiring more patients and longer follow-up — than studies trying to prove that one treatment is better than another, Brawley said.

About 15 percent of women with early breast cancer have tumors that respond to Herceptin, also called trastuzumab. Such tumors are particularly aggressive, because they have high levels of a protein called HER2, which promotes cancer growth. The drug significantly increases survival in those women.

But it has risks as well, particularly heart problems, which are sometimes permanent.

“I have personally seen congestive heart failure caused by Herceptin,” Brawley said. “The longer you give it, the likelier they are to get it. So it’s a wonderful thing if you can give it for a shorter time.”

In the United States, 266,000 new cases of invasive breast cancer are expected in 2018, and nearly 41,000 deaths. Globally, the most recent statistics come from 2012, when there were 1.7 million new cases.

The women in the study had early-stage breast cancer, meaning it had not spread to bones or organs — stages 1, 2 and 3. The findings do not apply to women with more advanced disease that has spread, Stage 4. Those patients need a longer course of treatment, Earl said.

She said the findings would undergo “rigorous scientific scrutiny” by other researchers and be published in a peer-reviewed journal.

In addition, the results will be analyzed further to determine whether there are subgroups of patients with specific levels of risk that would signal different advice about Herceptin.

“The final call will be with our colleagues and patients to decide whether these results will change practice,” Earl said. “This could be absolutely practice-changing for a lot of patients,” said Dr. Jennifer Litton, an associate professor of breast medical oncology at MD Anderson Cancer Center in Houston.

But she added, “I’d like to see the data, and see it peer-reviewed, before I make a big practice change.”

In the meantime, the results should reassure women who in the past had to quit Herceptin after only six months because of side effects, Litton said.

She had a patient like that whom she had worried about. “Now I don’t feel bad,” Litton said.

Earl’s study, called the Persephone trial, included 4,089 women in Britain who were picked at random to take the drug for six or 12 months, along with standard chemotherapy. The women were 23-82 years old, with a median age of 56. They were followed for a median of more than five years.

After four years, the disease-free survival rate was 89.4 percent in those treated for six months, and 89.8 percent in the 12-month group.

Disease-free survival means they had no signs of breast cancer, and the lack of difference between the two groups suggests that their overall survival should be equal as well, Johnson said, though longer follow-up would be needed to be sure.

Earl said they would be followed for 10 years. Toxicity can build up over time, and with the shorter course, half as many women had to quit treatment early because of heart problems: 4 percent in the six-month group, versus 8 percent in the 12-month group.

Earlier studies that proved Herceptin’s effectiveness treated patients for a year, a somewhat arbitrary duration, but one that became the standard of care because there was data to support it.

To change that standard, researchers had to produce evidence that it could be safely done. Earl’s study is the first step in that direction.