Oct. 1, 2021 -- One in 8.
Mention that statistic, and many women in the U.S. immediately know it refers to their lifetime risk of getting breast cancer.
Although the statistic may stir up anxiety, those diagnosed with breast cancer today have a more positive prognosis than ever, experts say. That's due to better understanding of the disease, wider choices of treatments, and more individualized treatment designed to reduce the risk of recurrence and lessen side effects.
While breast cancer incidence has risen by 0.5% per year in recent years, and it remains the second leading cause of cancer death in women, outpaced only by lung cancer, there are now more than 3.8 million breast cancer survivors in the U.S.
If the disease is caught early, women with breast cancer have a survival rate of an astounding 99%, though that may dip to 28% if the cancer has spread.
But despite the progress, much work remains. Read on to see how far we’ve come in the fight against breast cancer -- and what experts say needs to happen next.
Breast Cancer: Not a Single Disease
"Breast cancer is increasingly viewed as multiple different diseases," says Harold J. Burstein, MD, a breast oncologist at the Dana-Farber Cancer Institute in Boston.
That discovery, in turn, has helped to individualize treatment and predict exactly how much treatment is needed for a specific patient, he and other experts say.
Knowing the hormone status of breast cancer cells and analyzing the genes of cancer cells provide valuable information to guide treatment decisions. Cancer experts commonly speak of three subsets, Burstein says:
- Hormone receptor-positive cancer cells (estrogen receptor-positive or progesterone receptor-positive) have receptors that are sensitive to either estrogen or progesterone and can be treated with therapy that blocks the growth of the cells.
- HER2-positive cancer cells have too much of a protein called HER2, which can make cancers grow more quickly.
- Triple negative cancer cells test negative for estrogen receptors, progesterone receptors, and excess HER2 protein.
"We have seen progress in each of those three subsets in different ways," says Burstein, who’s also a professor of medicine at Harvard Medical School.
Molecular Diagnostics and ER-Positive Cancers
For ER-positive, which accounts for up to 75% of breast cancers, ''molecular diagnostics has transformed the way we think about early stage cancer and spared many women chemotherapy," Burstein says. He is speaking about genomics tests like OncotypeDX and others that analyze gene activity to predict how the cancer will behave. While genetic testing helps pinpoint the risk of getting cancers, genomics helps in choosing treatment once the cancer has occurred.
Depending on the analysis, he says, the tests have allowed doctors to recommend skipping chemotherapy for most women with these cancers detected at early stage. And no one likes chemotherapy, as Burstein notes.
Other good news for those with ER-positive metastatic cancers, which have a lower survival rate, are treatments with drugs known as CDK4 and CDK6 inhibitors. CDK4 and 6 are enzymes that are crucial to cell division. The inhibitor drugs, including palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio), work by interrupting the cancer cells' growth.
New Hope for HER2-Positive Cancers
HER2-positive breast cancers used to be highly concerning, but ''over 20 years, there's been a total flip-flop," Burstein says. These cancers are now among the most successfully treated, he and others say.
Treatment for these cancers has improved due to what is called targeted therapies, agrees Marina Sharifi, MD, a postdoctoral fellow in hematology, medical oncology and palliative care at the University of Wisconsin Carbone Cancer Center, Madison, who recently published a review on the treatments.
"These targeted therapies have really revolutionized our ability to treat this cancer," she says.
She is referring to drugs like trastuzumab, better known as Herceptin. It was approved by the FDA in 1998 and was the start of taking the HER2-positive breast cancers from a tough diagnosis to a manageable one. Herceptin is a monoclonal antibody -- a man-made protein that acts like a human antibody in the immune system -- that attaches to the HER2 protein, which is found in excess on the surface of cancer cells in this type of tumor. That helps the cancer cells stop growing.
Many more monoclonal antibody drugs are available now, and some are in use along with chemotherapy, an approach called an antibody-drug conjugate. The anti-HER2 antibody acts like a homing signal by attaching to the HER2 protein, and then it brings in the chemo to directly attack the cancer.
Immunotherapy for Triple Negative Cancers
"Immunotherapy is making an impact on triple negative cancers," says Yuan Yuan, MD, a breast oncologist and associate professor of medical oncology and therapeutics research at City of Hope Cancer Center in Duarte, CA.
The drug pembrolizumab (Keytruda) works with the immune system to stop T cells from hiding so they can do their job: detect and kill cancer cells. It's been used to treat lung cancer, head and neck cancers, and melanoma, among others. In studies in women with advanced triple negative breast cancer, it has extended survival in this tough-to-treat cancer, Yuan says. It can be combined with chemotherapy.
It's also being used for newly diagnosed, early-stage triple negative breast cancers, she says.
Expanded Genetic Testing
More women are likely to get genetic testing these days, Yuan says. Under expanded guidelines on breast cancer genetic testing issued in 2019 by the National Comprehensive Cancer Network, an alliance of 31 cancer centers, there is still a strong focus on testing for the BRCA1 and BRCA2 mutations long known to raise risk. But attention is also focused on including other gene mutations that have been found to make you more likely to get breast cancer.
Yuan says there are a good number of patients who carry genetic mutations that don't fit into the testing recommendations in the guidelines. In the future, genetic testing may be made more available for these patients, she says.
Right now, ''there are more mutations than the drugs we have [to treat them],” Yuan says.
Eventually, she hopes, an increase in drugs will make matching the mutations to the treatment easier.
Updated Guidelines for Surgery
In terms of surgery for breast cancer, ''one of the biggest advances is our understanding of breast pathology," says Matthew J. Piotrowski, MD, an assistant professor of breast surgical oncology at the University of Texas MD Anderson Cancer Center, Houston. That increased understanding, and a recent guideline, have changed breast-conserving surgery, better known as lumpectomy.
In 2014, three cancer organizations issued guidelines to settle debate about ideal margins of healthy tissue after excising a tumor during breast-conserving surgery.
"Before, everyone had their own idea of what was best," Piotrowski says. "Two millimeters? A centimeter?"
Under the guidelines, the consensus is that a wider margin does not mean better results in terms of less cancer recurrence or less risk of repeat surgery for cancer that was missed.
The tumor and surrounding tissue are rolled in a special ink so the outer edges or margins are visible. Surgeons call a margin with ink negative and one without ink positive or clear. After excising the tumor, if there is healthy tissue around the excision site, no matter how small, that's fine, under the new guidelines.
"We can have smaller margins and allow more women to be candidates for breast-conserving surgery," he says.
The guidelines were based on a review of 33 studies involving more than 28,000 patients and looked at how the margins affected recurrence rates, re-excision rates, and cosmetic effects.
Much Work to Be Done
In 2019, before the pandemic, 76.4% of women ages 50 to 74 had had a mammogram within the last 2 years, according to the National Cancer Institute. Then the pandemic hit, and one study found the number of mammograms was just 1% of expected volume in April 2020. By July2020, rates were up to 90% of pre-pandemic levels, but experts say there is still a deficit to make up.
"I have recently seen a lot of stage IV [breast cancer]," Yuan says, blaming the lack of screening during the pandemic.
Even with the progress in treatments, more is needed, especially for advanced cancers, experts agree.
Costs of cancer care are often still a ''huge problem," Burstein says.
After a cancer diagnosis, ''people are likely to work less, have a net decline in family or household income; those are real things that have real consequences, not just for the patients but their families."
Disparities in early detection still exist, he says.
"These track along very familiar lines of race and socioeconomic status," he says, and are not unique to breast cancer.
Patient Awareness, Access to Info Increase
On the plus side, patients' access to information has increased, says Kari B. Wisinski, MD, interim division chief of hematology, medical oncology, and palliative care at the University of Wisconsin Carbone Cancer Center. That's due to the 21st Century Cures Act, which gives patients access to doctors' notes. Patients can see test results and other information more easily and can be more engaged in their care, she says.
Awareness of clinical trials has also increased, she says, noting that these trials are viewed as more ''normalized and advocated for through social media."
And in time, that research promises to improve treatments and survival even more.