Study: Immunotherapy may lead to long-term remission of metastatic breast cancer

IN-DEPTH REVIEW OF RESEARCH

Study background:

Metastatic breast cancer is defined as breast cancer that has spread and formed tumors at distant places in the body. It may be a woman’s initial diagnosis (at stage 4) or develop as a recurrence after a stage 1, 2 or 3 breast cancer metastasizes.

Data from a 2017 SEER study (Mariotto, et al.) indicated that over 170,000 women in the U.S. are living with metastatic breast cancer (and there are also several hundred men with metastatic breast cancer). Five-year survival rates for metastatic breast cancer patients have increased. For ages 18-49, that rate rose from 18% between 1992-1994 to 36% between 2005-2012. During the same time, average survival for women ages 15-49 whose first diagnosis was metastatic breast cancer increased from 22.3 months to 38.7 months. Average survival time for women ages 50-64 whose first diagnosis was metastatic breast cancer increased from 19.1 months to 29.7 months.  

Despite longer life spans after diagnosis, many deaths due to metastatic breast cancer still occur annually. Based on Mariotto’s study, only about 17% of women with living with metastatic breast cancer have survived more than 10 years. Metastatic breast cancer can be difficult to treat because cancer cells spread to many parts of the body and often resist standard treatment. Finding new approaches or treatments to slow, halt or reverse cancer growth continues to be an active area of research.

One promising technique for treating metastatic cancer is adoptive cell therapy (ACT), also known as adoptive transfer. Researchers extract a patient’s own tumor-infiltrating lymphocytes (TILs); these are unique immune cells that can recognize and attack her tumor cells. These TILs are then grown to vastly larger numbers in the lab and then they are reintroduced into the patient. 

Adoptive cell transfer has been used successfully with melanoma and colorectal cancer. Approximately 50% of patients with metastatic melanoma who were treated with ACT have shown complete remission. Some types of ACT involve genetically modifying immune cells to boost their effectiveness against cancer cells. In this study, however, the patient’s cells were selected and allowed to multiple in the lab, but they were not genetically modified.

This study is very important because it is the first successful application of T-cell immunotherapy for late-stage breast cancer. It holds hope of a new treatment approach that resulted in complete remission of one woman's metastatic breast cancer. Such a complete positive result is highly unusual.

Researchers of this study wanted to know: If treatment with a patient's own immune cells would lead to tumor remission.

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Population(s) looked at in the study:

This research is a case study of a 49-year-old woman with advanced metastatic breast cancer and an exceptionally effective treatment. Originally diagnosed at age 39 with DCIS in her left breast, she then had a modified radical mastectomy. She was in remission for 10 years before being diagnosed again with ER+, HER2- metastatic breast cancer with tumors in multiple locations, including several lymph nodes, her right breast and left chest wall. She then had several types of chemotherapy and endocrine therapies to treat her metastatic cancer that did not halt growth of her tumors.

Study findings:  

This study approach is based on immunotherapy—stimulating the body's own defense system to attack tumor cells. This happens naturally to some extent, but as cancer grows, a person’s immune system becomes overwhelmed and is less able to respond.

In this study, researchers collected two types of cells from the patient: tumor cells from a metastasis in the right breast and immune cells from the patient's blood. First, they identified unique proteins on the surface of the tumor cells. (These are different from the proteins of normal cells.) Because not all immune cells are alike, they then looked at the patient’s immune cells to identify the ones that could specifically target the tumor proteins. These selected tumor infiltrating lymphocytes, or TILs, were grown in large numbers in the lab and injected back into the patient, greatly strengthening her own body’s defense against her cancer.

The result was surprisingly effective: 6 weeks after treatment her tumors were reduced in size by 51%, and by 22 months after treatment, the masses in the woman's chest wall, right breast and lymph nodes were undetectable.

Limitations:

The largest limitation of this study is number of participants—it is a case study of just one patient. Melanoma treated by ACT is effective for 50% of patients treated; however, it is unclear what proportion of metastatic breast cancer patients would respond to this therapy. While this woman responded well and is living without detectable cancer, researchers cannot be sure if her response will be typical, whether it will vary, or if it is a fluke. This is part of an ongoing clinical trial and data from additional participants may be available in the near future.

Whether or not ACT is safe and effective is still unknown. Patients with other metastatic cancers who have been treated with ACT have experienced side effects. This patient experienced low blood phosphate levels, a high fever (associated with immune cell depletion), and other treatable major side effects during ACT. But the ACT did not appear to adversely affect her normal tissue. It is too early to know if other unintended side effects would occur when more patients are treated using this technique.

Another limitation of this study is that as part of the procedure, the patient was also treated briefly with the immunotherapy agent pembrolizumab once before ACT and three times after ACT. Pembrolizumab is considered a checkpoint block that can halt cancer cell growth to allow the immune system to attack the cancer more effectively. It is possible that the positive effects observed are due to this drug rather than the ACT treatment. However, historically, pembrolizumab does not have a significant effect on ER+ tumors like those in this patient. Furthermore, when researchers examined the tumor cells of this particular patient, the protein recognized by pembrolizumab was not present. Therefore, it seems unlikely that this drug accounts for the remission observed (although it may aid ACT effectiveness). Further ACT testing without this drug is needed to clarify this issue.

The patient treated is a younger woman (age 49) who does not have a hereditary mutation in a breast cancer predisposition gene. Whether or not her result will apply to women with hereditary mutations is unclear.

Conclusions:

This is an exciting and promising new technique. Much more data is needed to determine its safety and effectiveness and its potential limitations or side effects.

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Posted 8/16/18