Breast Cancer: Why Aggressive Isn’t Always Better

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By Mary Jacobs

This story originally appeared in the Dallas Morning News, April 2, 2018.

Just a decade or two ago, the battle cry for breast cancer patients was “Be aggressive.” Patient advocates urged women to insist on the most aggressive treatments available, which seemed to offer the best chance for remission and long-term survival.

Today, the new mantra for some might be “Back off.”

With a growing body of evidence that aggressive isn’t always better, manyoncologists are embracing “de-escalation” — a move away from chemotherapy and other harsh, traditional treatments, and toward targeted therapies with fewer side effects.

“We’ve probably treated too many women for too long with too many drugs,” said Dr. Carlos L. Arteaga, director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas. “Doctors are seeing that it’s time to start de-escalating, without compromising a good outcome.”

A better arsenal

De-escalation takes many forms: prescribing less toxic treatments; opting for lower doses of medication or shorter duration of radiation treatment; withholding drugs with no proven additional benefit.

Dr. Philip Kovoor, medical director of oncology at Baylor Scott & White Medical Center in Plano(Baylor Scott & White Medical Center)
Dr. Philip Kovoor, medical director of oncology at Baylor Scott & White Medical Center in Plano (Baylor Scott & White Medical Center)

It’s fueled by a better understanding of different subtypes of tumors, a wider array of newer treatments, better data on how to minimize dosage without compromising the patient’s chances for a cure or remission, and a push to factor patient quality-of-life into the treatment decision.

“We have a better arsenal today,” said Dr. Philip Kovoor, medical director of oncology at Baylor Scott & White Medical Center in Plano. “De-escalation is a factor of learning more about the biology of cancer and becoming more personalized about how we administer therapy.”

Thirty years ago, doctors had three weapons to fight breast cancer: surgery — mastectomy or lumpectomy; radiation; and chemotherapy, typically a cocktail of cytotoxic drugs that killed cells, healthy as well as cancerous, and caused side effects like nausea, low blood counts, nerve damage and kidney problems.

Concerns about the trend

“De-escalation” has become such a buzzword, often turning up in medical journals, that some doctors worry that the pendulum could swing too far.

While solid data guides the trend, there are few comparative, double-blind clinical trials that directly measure the results of newer treatments against those of chemotherapy or traditional treatments. A 2017 conference of German breast cancer specialists adopted the motto “Escalating and De-Escalating” with an eye toward reducing over-treatment as well as under-treatment through carefully individualized regimens.

The panel recommended intensifying radiation therapy, for example, for a specific group of high-risk patients, but not for low-risk patients.

The zenith of the aggressive approach came in the 1990s, when doctors tried bone marrow transplants with high-dose chemotherapy for some breast cancer patients. The results were ultimately disappointing.

Dr. Carlos L. Arteaga, director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center.(UT Southwestern Medical Center)
Dr. Carlos L. Arteaga, director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center. (UT Southwestern Medical Center)

“That idea was based on our best knowledge at the time,” Arteaga said. “But in 15 to 20 years, we will likely consider bone marrow transplants very primitive.”

In the 1990s and early 2000s, new treatments emerged, including targeted therapies (such as monoclonal antibodies and protein inhibitors), hormone and biologic therapies as well as new chemotherapies — most of them more easily tolerated than traditional chemotherapy. Advances in genetics led to the molecular profiling of tumors, giving oncologists better insights to match treatments more precisely to each patient’s subtype.

When aggressive treatment was prevalent 20 to 30 years ago, Kovoor says, mortality rates were much higher. “The battle cry was, ‘We’ve got to hit this with everything we have,'” he said. “Now, we have a better understanding of the biology and we’re wiser. We’re thinking more in terms of ‘What’s the most effective and least toxic way of managing a cancer diagnosis?'”

Chemotherapy: still around

De-escalation mostly applies to patients with early-stage breast cancer — yet another reason to promote early detection. All of the doctors interviewed for this story cautioned that chemotherapy still has a place in the toolbox of cancer treatments, especially for those with metastatic disease, when the cancer has spread to other areas of the body.

Dr. Nisha Unni, a medical oncologist at UT Southwestern Medical Center.(UT Southwestern Medical Center)
Dr. Nisha Unni, a medical oncologist at UT Southwestern Medical Center. (UT Southwestern Medical Center)

Arteaga worries that de-escalation could make some patients even more frightened of chemotherapy, which still saves lives. And there’s still plenty of debate, Kovoor notes, about when to prescribe chemotherapy, especially for patients in the gray area between high risk or low risk for recurrence.

“There is still a role for chemo. We’re just getting smarter about identifying those patients that don’t need chemo or don’t need as much of it,” said Dr. Nisha Unni, a medical oncologist at UT Southwestern Medical Center.

What has changed, Arteaga says, is that chemotherapy has moved to the back of arsenal for some subtypes of breast cancer.

“If we look at those with early stage, operable breast cancer, the majority are going to be cured without chemo,” he said. “Chemo stopped being the first option for treatment. Now it might be the fifth option.”

‘Kind of a blip’

Catrina Szende, 69, benefited from this de-escalated approach. In 2015, she was diagnosed with HER2-positive breast cancer. About 1 in 5 women with breast cancer have this subtype.

HER2-positive cancers tend to grow and spread aggressively, but Szende’s tumor was small — less than 1 centimeter in diameter.

“Before 2013, we would have prescribed Herceptin plus two very strong chemotherapies with a lot of side effects, Taxotere and carboplatin,”said Unni, who is Szende’s physician. But a 2013 study showed good results for patients with small tumors — 3 cm or less — who received a less toxic regimen of Herceptin and a low dose of Taxol, a chemotherapy.

Patients on this treatment had excellent disease-free survival rates with few side effects. A more recent update found that, of the 400 women in the study, only eight died, none due to cancer. For Szende, Unni recommended 12 weeks of Taxol, 12 months of Herceptin, plus a course of radiation.

Szende was initially skeptical about further treatment. She felt the surgery likely removed all traces of the cancer, and she didn’t relish the idea of battling nausea and other debilitating side effects of chemo.

“I thought seriously about refusing because I felt fine and had no symptoms,” Szende said. “But then I considered my two grown children and my grandchild, and thought, ‘I think they want me to be around a little longer.’ I owed it to them.”

Szende consulted with a second physician, who prescribed exactly the same regimen as Unni, so she agreed to the treatment. She worked in her job as a pharmacist throughout the 12 months of treatment; her co-workers had no idea she’d been ill. She did lose her hair, but had no other side effects. Today she’s in remission and in good health, and credits early detection and the new, less toxic treatment.

“While I was in treatment, a doctor told me I’d look back on this three years later as just a blip,” she said. “I thought he was being disrespectful. But now that I’m three years out, it is kind of a blip.