Treatment, not screening, credited with latest breast cancer advances

In In The News by Barbara Jacoby

By: Jill Daly


Women who get a diagnosis of breast cancer often have little preparation for what comes next, except in stories from their friends, their neighbors, their sisters, their mothers.

The good news is that women are surviving cases that years ago were resistant to even the most rigorous treatments. Breast cancer specialists in Pittsburgh say testing and treatment in recent years have become much more individualized — and effective — than in the past and that trend is progressing quickly.

Surgeries are often less invasive and radiation and other therapies are tailored to a woman’s individual case.

“At all levels of treatment, we’re doing really well,” said oncologist Adam Brufsky, medical director of the Women’s Cancer Center at Magee-Womens Hospital of UPMC. “The majority of patients in my office for breast cancer are going to survive. We try to get to that place with as little interference in their lives as possible.”

Although death rates have steadily declined since 1989, the chance of dying remains: The American Cancer Society estimates that 40,610 women will die of breast cancer in 2017.

Women often find out that they have suspected breast cancer after a mammogram. However, the most fast-growing, aggressive cancers develop within a single year and often aren’t detected in a screening. At the same time, mammography has become so sensitive that even small, slow-growing tumors that may never endanger a woman’s life are being detected.

Limits of screening

Researchers from the Yale Cancer Center published a study earlier this month on the dilemma of overdiagnosis as a result of mammography and explored why screening is not making more of a difference in reducing deaths from aggressive cancers.

The Yale analysis of national data on women with invasive breast cancer found many who had good prognoses for survival because their tumors were very small (less than 1 centimeter in diameter) and had other favorable features, such grade 1 status and estrogen- and progesterone-receptor status (if it’s positive, hormone therapy can help).

Lead author and surgeon Donald R. Lannin, professor of surgery at Yale School of Medicine, said the study was an extension of earlier work by H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice.

“We used his figure of 22 percent of invasive cancer is overdiagnosed. He didn’t really estimate which type of cancer is overdiagnosed or which group of patient. We think we have some models to get a pretty good idea of how overdiagnosis works and which patients are likely to be overdiagnosed.”

The study found cancers with the most favorable prognoses — predicting best survival — were those of grade 1 (cells that grow or spread slowly) along with one or more types of positive hormone-receptor status, for either estrogen or progesterone. Researchers didn’t gauge tumors’ HER2 status — it’s a growth-promoting protein found on cancer cells now treated with drugs that target HER2.

Groups with the worst survival were grade 2 tumors with no type of hormone receptor and grade 3 tumors lacking at least one of the two types.

A tumor’s size and its biological characteristics had a major influence on a woman’s prognosis. But large tumors with favorable features had a better prognosis than small tumors with unfavorable features, the study reported.

In women 40 years and older, tumors with favorable features made up 38.2 percent of tumors 1 centimeter in diameter or less, but only 9 percent of the tumors more than 5 centimeter.  Unfavorable features made up only 14.1 percent of 1 centimeter or less — and went up to 35.8 percent of tumors more than 5 centimeter.

“If we look at small cancers, a lot of the small cancers have the favorable biology and very few of the large,” Dr. Lannin said, “The opposite is also true: among the very aggressive, few are small … What is interesting is that for 100 years, we’ve known that small cancers have much better prognosis. We always thought that catching them earlier was better.”

The new conclusion is something else, he said: “Small cancers have a very good prognosis because they’re biologically favorable to begin with.”

Dr. Brufsky said opinions are divided over the Welch research on overdiagnosis as a result of screening mammography.

“For over 30 years we’ve been telling people that mammography saves lives. Welch said if it was saving lives, the number of aggressive tumors would be going down, but it’s not.”

He said the finding that most women over 40 have a good prognosis, regardless of the size of the tumor, means that many of the smaller tumors detected earlier would not be likely to become aggressive later.

“What that means is mammography is picking up really good-prognosis tumors.”

Research and profiles

But until testing can tell a woman that her tumor falls into that category, she will get that surgery. And researchers will continue to look for ways to minimize side effects and treatment, said Allegheny Health Network breast surgeon Michael Cowher.

The local nonprofit NRG Oncology continues the work, pulling together the research done by the National Surgical Adjuvant Breast and Bowel Project (with its operations center at Allegheny General Hospital and biostatistical center at the University of Pittsburgh), the Radiation Therapy Oncology Group and the Gynecologic Oncology Group.

Dr. Cowher and Dr. Brufsky said the Yale study’s use of biological factors was limited. There are now additional biomarkers, such as HER2 status and gene-expression profiling, using tests such as Mammaprint, Oncotype DX and EndoPredict. They can predict how well the cancer will respond to individualized treatment.

“No. 1, your cancer is not the same as someone you know who had cancer,” Dr. Cowher said. “That’s the beauty of genomic testing.” Profiling a tumor’s biological makeup and a patient’s individual health factors may someday allow doctors to avoid surgery in low-risk cases, he said.

“One way we might look at that in the future is we would do repeat biopsies, instead of surgery and radiation. As long as things stay stable, we might avoid operating.”

Individualized care

Dr. Lannin said the Yale finding that overdiagnosis happens mostly in older women should be an incentive to consider less treatment in cancer with a favorable prognosis.

Research has already led to less intensive treatment in some cases. Dr. Cowher recommended patients join a clinical trial, saying outcomes are often better for participants.

The least aggressive treatment now still starts with surgery, a lumpectomy, Dr. Brufsky said. If the patient is older and has lymph nodes testing negative for cancer, she might not need radiation. Hormonal therapy then might be considered, he said. “Then if it’s really aggressive, we think about chemotherapy.”

He said about 15 percent of cancers have a favorable prognosis. Being able to detect the slowest-growing among them would change treatment decisions. In the future, he said, each cancer will have “a genetic fingerprint” that points to the most effective treatment for each woman.