Unpacking the Current Treatment Options for Metastatic Breast Cancer

While breast cancer remains the most common cancer in women and the 2nd leading cause of cancer-related death in women in the U.S., researchers have also made leaps and bounds of progress in decreasing death rates since 1989, an expert explained.

“I think one of the things that we've done a really good job with is getting the word out about the importance of screening, mammography and finding cancers earlier, and that absolutely has contributed to lives saved,” said Dr. Reshma Mahtani, associate professor of medicine and co-leader of breast cancer program at Sylvester Comprehensive Cancer Center, University of Miami. “However, a lot of the improvements in our mortality rates are also directly linked to improvements in our therapies, especially novel therapies, newer treatments.”

Mahtani gave an overview of progress and updates in treatment of metastatic breast cancer at the recent CURE® Educated Patient® Breast Cancer Summit.

When a patient’s disease reaches a higher stage, in particular with stage 4 breast cancer, the five-year survival rate tends to drop off.

“But the take-home point is that many factors affect a patient’s outlook, such as their age, their health, the presence of hormone receptor status on the tumor cells, the treatments that are received and how well the cancer responds to those treatments,” Mahtani explained.

So, what happens when a patient’s breast cancer is metastatic?

From a general standpoint, metastatic disease is not “curable.” However, many patients can still go on to live with their cancer under control for a long period of time. Oncologists tend to focus on prolonging overall survival in these patients while also maintaining quality of life – meaning they try to find ways to improve symptoms and delay disease progression.

Current Strategies for Metastatic Breast Cancer

The current oncology “toolbox” has several different options for patients with metastatic breast cancer. They can be treated with endocrine therapy, chemotherapy or biologically targeted treatment.

“Endocrine therapy, or anti estrogen therapy, is one of our oldest targeted treatments in oncology,” Mahtani said. “And there is a bit of a misnomer, because women come and they say, ‘I have an estrogen driven cancer, why are you giving me hormone therapy?’ And so we call it hormonal therapy, but it's actually anti-hormonal therapy, because what we're trying to do is choke off that fuel supply to the cancer.”

There are several different options for estrogen therapy, including drugs like Soltamox (tamoxifen), which bind to the estrogen receptor or aromatase inhibitors to decrease estrogen production.

ER-Positive Breast Cancer Options

“Our treatment for metastatic ER-positive breast cancer is initially hormonal therapy and we always shut down the ovaries of a pre-menopausal woman in addition to that hormonal therapy as first-line treatment,” Mahtani said. “And in postmenopausal women, we know that aromatase inhibitors tend to be more effective than tamoxifen in in controlling the disease.”

However, most women tend to do well for a period of 10-14 months before their cancer begins to change and become resistant to the hormone blockade. This is what led to the development of targeted therapies to prolong the success of anti-estrogen medications.

With the development of several new agents in the stage 4 setting, patient outcomes have seen progress in recent studies, Mahtani explained.

“When you give anti-estrogen therapy with an aromatase inhibitor and add one of these targeted new or novel treatments, (Verzinio; abemaciclib), (Kisqali; ribociclib) or (Ibrance; palbociclib), you see a doubling in the amount of time that the cancer is controlled… so certainly we've made progress in not only controlling the disease for a longer period of time, but actually also allowing women to live longer, and these drugs have now become standard of care for estrogen driven metastatic breast cancer.”

Targeted approaches allow patients to experience less difficulties in terms of side effects, Mahtani added.

“These drugs are cell cycle inhibitors – they kind of make the cell sleepy, put it to sleep – it doesn't kill it off,” she said. “So when you stop the medication, the cell wakes back up very quickly, and you don't run into problems at the same degree that you would with chemotherapy, meaning with low white count and the need for IV antibiotics and being in the hospital with a fever.”

Approaches for HER2-Positive Breast Cancer

For HER2-positive breast cancer, there are multiple drugs that can target the HER2 protein. However, there is a substantial unmet need for these patients, Mahtani said.

There are currently two approved antibody drug conjugates for HER2-positive breast cancer. An antibody drug conjugate is a unique way of delivering chemotherapy, in which it is internalized in the cancer cell, then released to kill the cell.

“(It) may even drift out of the cell and kill off neighboring cells that have some of that HER2 protein,” she added.

While treatment options have evolved rapidly for HER2-positive breast cancer in the past 20 years, researchers continue to work on developing better options, “even in the face of a pandemic,” Mahtani acknowledged.

Triple-Negative Breast Cancer

Better treatment options are also on the horizon for triple-negative breast cancer – with a recent Food and Drug Administration (FDA) approval of Trodelvy (sacituzumab govitecan) for patients who have had two or more prior lines of chemotherapy, with at least one in the metastatic setting.

The FDA also granted an accelerated approval for an immunotherapy option for the metastatic setting – which was Keytruda (pembrolizumab) in combination with chemotherapy. Patients on this treatment saw an improvement in long-term outcomes, Mahtani said.

Genetically Driven Breast Cancer

PARP inhibitors, which are oral drugs, are also available and can be useful for genetically driven breast cancers. Two PARP inhibitors used to treat patients with stage 4 breast cancer who have a germline BRCA that showed promise were Talzenna (talazoparib) and Lynparza (olaparib).

“Both of these agents were compared against treatment of physicians choice chemotherapy and shown to be more effective in controlling the cancer and somewhat better tolerated,” Mahtani said.

In general, though, Mahtani stressed that regardless of your disease stage or type, it’s important to ask your oncologists as many questions as possible.

“I think it's very important that patients should feel empowered to be actually a member of the treatment team,” she said. “Your preferences, your lifestyle, your attitudes about what you will and will not be willing to accept in terms of toxic side effects like hair loss and other things absolutely need to be heard and valued. And so with that, my goal is to have you all feel empowered to ask the right questions.”

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