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Adding Surgery to Treatment Plan Offers Better Survival for Certain Women Diagnosed With Stage IV Breast Cancer

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A combination of surgery and systemic therapy can improve survival more than systemic therapy alone for women diagnosed with stage IV breast cancer with known hormone receptor and HER2 status, according to a study.

The research was published in the May 2021 issue of the journal Annals of Surgical Oncology. Read the abstract of “Benefits of Surgical Treatment of Stage IV Breast Cancer for Patients With Known Hormone Receptor and HER2 Status.”

Systemic treatments travel throughout the body destroying cancer cells. Chemotherapy, hormonal therapy, and targeted therapies are considered systemic treatments. But for this study, the researchers defined systemic therapy as chemotherapy or hormonal therapy.

Stage IV vs. metastatic
Treatment for stage IV breast cancer
About the study
What this means for you

Stage IV vs. metastatic

Stage IV describes invasive breast cancer that has spread beyond the breast and nearby lymph nodes to parts of the body away from the breast, such as the lungs, bones, liver, or brain. If breast cancer is stage IV at first diagnosis, it’s called “de novo” by doctors. About 6% of breast cancers are de novo.

“Metastatic” and “advanced-stage” are other terms used to describe stage IV breast cancer.

Still, certain groups make a distinction between stage IV breast cancer and metastatic breast cancer. The American Cancer Society (ACS) and the National Cancer Institute (NCI) both say that a cancer’s stage doesn’t change after a diagnosis. So, if a person is diagnosed with stage II breast cancer and then a few years later the cancer comes back in the bones, the diagnosis is technically stage II breast cancer with metastatic recurrence to the bones.

But this is not how most people — or even most oncologists — talk and think about cancer. When someone is diagnosed with breast cancer that comes back in a part of the body away from the breast, people and doctors usually consider that cancer to be stage IV/metastatic.

The ACS and NCI say that a cancer’s stage doesn’t change when there is recurrence so they can compile statistics on cancer outcomes. These organizations follow people over time and keep track of:

  • the number of people diagnosed with a particular stage of cancer who have a recurrence
  • the type of recurrence

At Breastcancer.org, we talk about breast cancer the way most doctors do. So, like the American Society of Clinical Oncology (ASCO), we use the terms “stage IV” and “metastatic” interchangeably. We also consider a person who has a metastatic recurrence to have stage IV cancer.

In the study reviewed here, all the women had de novo breast cancer, meaning the cancer was stage IV at first diagnosis. So the results apply to only that type of breast cancer.

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Treatment for stage IV breast cancer

Systemic treatments, such as chemotherapy, hormonal therapy, and targeted therapies are commonly used to treat stage IV breast cancer. The cancer’s characteristics determine which of these treatments makes the most sense.

Nearly all stage IV breast cancer is treated with some type of chemotherapy. If the cancer is hormone-receptor-positive, it almost always is treated with hormonal therapy. As the name implies, targeted therapies target specific characteristics of cancer cells, such as the HER2 protein that tells cancer cells to grow in a rapid or an abnormal way. So cancer that is HER2-positive is almost always treated with an anti-HER2 targeted therapy.

Previous studies have looked at whether adding surgery to the treatment plan for stage IV disease can improve outcomes. Still, the results have been mixed.

The researchers who did this study wanted to see if adding surgery to systemic treatments would improve survival for women diagnosed with specific types of stage IV breast cancer.

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About the study

The researchers used the National Cancer Database (NCDB) to identify 12,838 women diagnosed with de novo stage IV breast cancer between 2010 and 2015. The NCDB is a joint project of the American Cancer Society and the American College of Surgeons. The database includes information from Commission on Cancer–accredited facilities and includes more than 70% of all new cancer diagnoses in the United States.

The hormone receptor status and HER2 status was known for all the cancers. All the women had received treatment with systemic therapy, meaning they had received treatment with chemotherapy, hormonal therapy, or both.

The study excluded women who:

  • died in the first 6 months after diagnosis
  • were diagnosed with breast cancer with unknown hormone receptor or HER2 status
  • didn’t receive systemic treatments

Overall, about 72% of the women in the study were white and about 18% were Black. Most of the women:

  • had insurance
  • lived in a metropolitan area
  • had no other medical conditions, such as high blood pressure or diabetes
  • were diagnosed with estrogen-receptor-positive, progesterone-receptor-positive, HER2-negative stage IV breast cancer

When the researchers looked at the types of treatments the women received, they found:

  • 6,649 women were treated with only systemic therapy
  • 2,906 women were treated with systemic therapy and radiation therapy
  • 1,689 women were treated with systemic therapy and surgery
  • 1,594 women were treated with systemic therapy, radiation therapy, and surgery

Overall, the results showed that women who had surgery had better 5-year survival rates than women treated with only systemic therapy. Women treated with surgery, systemic therapy, and radiation therapy had the best survival rates.

For all the women in the study, 5-year survival rates were:

  • 38% for women treated with systemic therapy, radiation therapy, and surgery
  • 32% for women treated with systemic therapy and surgery
  • 21% for women treated with only systemic therapy
  • 19% for women treated with systemic therapy and radiation therapy

These differences in survival rates were statistically significant, which means they were likely due to the difference in treatment and not just because of chance.

The researchers then looked to see if surgery affected survival rates based on HER2 status.

For the 931 women diagnosed with HER2-positive disease, surgery also improved survival. Among this group, 5-year survival rates were:

  • 48% for women treated with systemic therapy, radiation therapy, and surgery
  • 41% for women treated with systemic therapy and surgery
  • 29% for women treated with only systemic therapy
  • 21% for women treated with systemic therapy and radiation therapy

These differences in survival also were statistically significant.

The researchers noted that survival rates for women diagnosed with HER2-positive disease were higher than survival rates for all the women in the study collectively.

Finally, for the 3,283 women who had surgery, the researchers looked to see if having chemotherapy before or after surgery affected survival rates.

Doctors call treatments given before surgery neoadjuvant treatments and treatments given after surgery adjuvant treatments. So chemotherapy before surgery is neoadjuvant chemotherapy, and chemotherapy after surgery is adjuvant chemotherapy.

Overall, the researchers found that women diagnosed with hormone-receptor-positive, HER2-positive stage IV breast cancer had better survival rates if they received chemotherapy before surgery rather than after surgery.

Looking specifically at HER2 status, 5-year survival rates were:

  • 55% for women diagnosed with HER2-positive disease who received chemotherapy before surgery
  • 35% for women diagnosed with HER2-positive disease who received chemotherapy after surgery
  • 34% for women diagnosed with HER2-negative disease who received chemotherapy before surgery
  • 30% for women diagnosed with HER2-negative disease who received chemotherapy after surgery

These survival differences were statistically significant.

Looking specifically at estrogen receptor status, 5-year survival rates were:

  • 42% for women diagnosed with estrogen-receptor-positive disease who received chemotherapy before surgery
  • 30% for women diagnosed with estrogen-receptor-positive disease who received chemotherapy after surgery
  • 30% for women diagnosed with estrogen-receptor-negative disease who received chemotherapy before surgery
  • 22% for women diagnosed with estrogen-receptor-negative disease who received chemotherapy after surgery

These survival differences were statistically significant.

Looking specifically at progesterone receptor status, 5-year survival rates were:

  • 45% for women diagnosed with progesterone-receptor-positive disease who received chemotherapy before surgery
  • 32% for women diagnosed with progesterone-receptor-positive disease who received chemotherapy after surgery
  • 32% for women diagnosed with progesterone-receptor-negative disease who received chemotherapy before surgery
  • 25% for women diagnosed with progesterone-receptor-negative disease who received chemotherapy after surgery

These survival differences were statistically significant.

“In conclusion, this large, multicenter study using data from the NCDB demonstrated that for patients with stage IV breast cancer, systemic therapy with surgical intervention was beneficial to survival, and surgical intervention after [neoadjuvant chemotherapy] for [estrogen-receptor-positive], [progesterone-receptor-positive], and HER2-positive patients was associated with significant survival benefit,” the researchers wrote.

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What this means for you

It’s important to know that this study only looked at women who were diagnosed de novo, meaning the breast cancer was stage IV at first diagnosis. So the results only apply to that type of breast cancer. It’s not clear if surgery would improve survival for women diagnosed with a metastatic recurrence — or breast cancer that has spread to other parts of the body away from the breast during treatment for early-stage disease.

If you’ve been diagnosed with stage IV breast cancer, this study strongly suggests that adding surgery to your treatment plan may improve survival. It also suggests that having chemotherapy before surgery offers better chances of survival than chemotherapy after surgery.

After a diagnosis of stage IV disease, you and your doctor have a number of treatment options to consider, including chemotherapy, hormonal therapy, targeted therapy, immunotherapy, radiation, and surgery. Your treatment plan depends on the characteristics of the cancer, as well as any other health conditions you may have and your personal preferences.

If your doctor doesn’t recommend surgery for you, you may want to bring up this study and ask why surgery isn’t in your treatment plan.

Together, you and your doctor can develop the best treatment plan for your unique situation.

Visit Metastatic Breast Cancer for more information.

To talk with others with a similar diagnosis, visit the Discussion Board forum StageIV/Metastatic Breast Cancer ONLY.

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Written by: Jamie DePolo, senior editor


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