What doctors want women to understand about breast cancer and genetics

More than 50 years of progress against breast cancer can be summed up in two numbers many patients never hear. In the 1970s, the five-year survival rate was in the 70% range, said Dr. Alberto Montero, a medical oncologist, associate professor of medicine at the Case Western Reserve University School of Medicine, and clinical director of the Breast Cancer Medical Oncology Program at University Hospitals Seidman Cancer Center. Today, he said, it is above 95%, and early detection is a major reason why.

That is the main message Montero hopes people take away: breast cancer is often highly treatable when it is found early. Mammography can detect small tumors, and outcomes are closely tied to how soon the disease is caught.

The National Cancer Institute's SEER program reports five-year relative survival of 91.9% for women diagnosed with breast cancer between 2016 and 2022, compared with roughly 76% for women diagnosed in the mid-1970s. Survival changes dramatically depending on how far the cancer has spread. About 64% of cases are found while still limited to the breast, and five-year relative survival for that group is 100%, meaning those women are, on average, just as likely to be alive five years later as women who never had breast cancer.

Based on an interview with Montero, this article from Case Western Reserve University School of Medicine looks at what screening recommendations actually mean, why most cases are not caused by inherited mutations, and how molecular testing now helps determine who can avoid chemotherapy.

What the screening guidelines actually cover

Montero said mammography remains the standard against which other screening tools are measured. “It's still the gold standard,” he said. In his view, the basic recommendation is a mammogram beginning around age 40.

He also emphasized a point he said is often missed: those guidelines are intended for women at average risk. Someone with a strong family history or a known genetic mutation follows a different path, and a doctor can help determine her true risk.

Recommendations from major groups have largely aligned around age 40, although they still differ on how often screening should happen:

• The U.S. Preventive Services Task Force recommends starting at 40 and getting a mammogram every other year through age 74 for women at average risk.
• The American Cancer Society says women should have the option to begin annual screening at 40, with regular screening for all women starting at 45.
• Neither set of guidance applies to women at high risk, who are typically screened earlier, more often, or with additional imaging.

Not one disease, but at least four

More from this section

“Breast cancer is indeed not just one kind of cancer,” Montero said. “I think that's another thing that a lot of people may not understand.” He said better science and molecular testing have shown that breast cancer has at least four major subtypes, each with different treatment approaches and natural histories.

Researchers generally group those subtypes as luminal A, luminal B, HER2-enriched and basal-like, the last of which overlaps heavily with triple-negative breast cancer, according to Susan G. Komen. The organization says treatment decisions are driven mainly by stage, grade, hormone receptor status and HER2 status rather than the molecular subtype label alone, though the two usually closely match.

Genetics explains less than most people assume

When asked who should be tested for inherited risk, Montero began by correcting a common assumption. “The important thing to know is that 90% of women who have breast cancer don't have a genetic cause,” he said.

Hereditary cases make up only a small portion of the total. About 5% to 10% of breast cancers are tied to inherited gene mutations, most commonly BRCA1 and BRCA2. Carrying one of those mutations matters greatly for the person who has it. More than 60% of women with a harmful BRCA1 or BRCA2 change develop breast cancer in their lifetime, compared with about 13% of women in the general population, according to the National Cancer Institute. Testing has expanded to reflect that risk. A guideline from the American Society of Clinical Oncology and the Society of Surgical Oncology recommends offering BRCA1/2 testing to every patient newly diagnosed at 65 or younger, and to selected patients older than 65 based on family history, ancestry, tumor type or eligibility for certain drugs.

Deciding who can skip chemotherapy

The same molecular tools used to classify breast cancer are now helping doctors decide how aggressively to treat it. “Before, we used to give chemo to almost any patient who had a tumor above a certain size,” Montero said. “Now we can do genetic testing, and we can understand who has a higher risk cancer or a lower risk cancer and who needs chemotherapy, who doesn't need chemotherapy.”

The evidence for that shift came from TAILORx, a trial involving 10,273 women with hormone-receptor-positive, HER2-negative, node-negative breast cancer. Researchers used a 21-gene assay to score each tumor. Among the 9,719 participants with follow-up data, 69% fell in the middle range, and for them, hormone therapy alone worked as well as hormone therapy plus chemotherapy, with some chemotherapy benefit still seen in women aged 50 and younger. It was the largest breast cancer treatment trial done at that point, and the results were published in the New England Journal of Medicine in 2018.

For Montero, that reflects where the field is headed. “There's a lot of progress in being able to personalize a treatment for patients so that they get only the treatments that they need,” he said, “and they avoid any toxic treatments that they might not need.”