Tag: Triple-Negative

Extending Life with Immunotherapy: Advances in Treating Triple-Negative Breast Cancer

The August 9, 2022 edition of the National Cancer Institute’s Cancer Currents blog announced the findings of the clinical trial KEYNOTE-355 that examined the benefits of using the immunotherapy drug pembrolizumab (Keytruda) in conjunction with chemotherapy in treating advanced triple-negative breast cancer (TNBC).

The results, published in the New England Journal of Medicine (Cortes et al., 2022), revealed that pembrolizumab in conjunction with chemotherapy was effective in extending the lives of TNBC patients with advanced disease as compared to chemotherapy alone, and the difference was striking. Those who received the drug lived a median of 23 months compared to 16.1 months for the chemo-only group.

Sources: Cancer.gov, Cancer Currents blog

Of course, cancer differs among patients and not all TNBC tumors are the same. The life-prolonging benefits of pembrolizumab were limited to those patients with PD-L1 scores of at least 10; PD-L1 is an immune checkpoint protein, and the score denotes the level of this protein found in cancer tumor cells.

And it’s important to note that while the drug extended life expectancy, it was not yet a cure, which is what we’re all still waiting for.

So there are asterisks associated with these findings, which might be disappointing for those with advanced cancers of this type. But the researchers stressed that this is a very promising outcome.

Consider the advances that have been made. TNBC used to be treated with untargeted therapies, kind of like throwing everything you’ve got at the tumor and hoping that something “sticks”. On the other hand, pembrolizumab is a targeted therapy for this specific subset of TNBC, and that makes a huge difference.

There has been a push to address the complexities of TNBC and large strides have been made in understanding what makes it tick. New therapies are being approved and they are making researches optimistic about eventually being able to cure the disease.

As an example, in April 2021, the FDA approved the use of sacituzumab govitecan (Trodelvy) for the treatment of certain types of TNBC (after conditional approval had been granted in April 2020). As noted in the May 12, 2021 edition of the Cancer Currents blog, sacituzumab is comprised of an “antibody coupled to a more potent form of the chemotherapy drug irinotecan (Camptosar). The antibody binds to breast cancer cells, delivering the chemotherapy directly to those cells.”

There’s good news for some patients with advanced triple-negative breast cancer.

Notably, patients receiving sacituzumab lived a median of 11.8 months longer compared to 6.9 months for those patients receiving the chemotherapy alone. Positive results were also obtained for patients with brain metastases, where the cancer has spread to the brain, who tend to have worse outcomes when treated only with chemotherapy.

There is still so much more to learn. Cancer is a puzzle and researchers have known for some time that the pieces do not yet fit together cleanly. But each one of these advances brings us more effective treatments for TNBC, addressing more specific targets on the tumors. Lifespans are increasing and for many, cancer is taking the form of a chronic disease, not a death sentence.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~

REFERENCES

Cancer Currents Blogs

Sacituzumab Govitecan Approved for Metastatic Triple-Negative Breast Cancer, Cancer Currents, May 28, 2020: https://www.cancer.gov/news-events/cancer-currents-blog/2020/fda-sacituzumab-govitecan-triple-negative-breast-cancer

Sacituzumab Govitecan Earns Full Approval for Triple-Negative Breast Cancer, Cancer Currents, May 12, 2021: https://www.cancer.gov/news-events/cancer-currents-blog/2021/sacituzumab-govitecan-tnbc-regular-approval

Pembrolizumab Improves Survival in Advanced Triple-Negative Breast Cancer, Cancer Currents, August 9, 2022: https://www.cancer.gov/news-events/cancer-currents-blog/2022/pembrolizumab-triple-negative-breast-cancer-improves-survival

KEYNOTE-355 Clinical Trial
(as of this posting, the full article is not yet available to non-subscribers)

Cortes et al. (2022) Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. New Engl J Med, 387, 217-226. 10.1056/NEJMoa2202809

Targeted Therapy? Yes, Please!

You cannot say that there is a “good” cancer to have. Because the only thing that would make the cancer that you have “good” is not having it in the first place.

But if that’s not the case, the next best thing is having a cancer with characteristics that serve as targets for drugs, enabling the use of “targeted therapy”. As described by the American Cancer Society, “Targeted therapy is a type of cancer treatment that uses drugs designed to ‘target’ cancer cells without affecting normal cells. …Targeted drugs can block or turn off signals that make cancer cells grow, or can signal the cancer cells to destroy themselves.”

Cancer treatment often means chemotherapy, but there are some targeted therapies available that are highly effective.

When talking about breast cancer, currently there are several targets possible: estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (or HER2 [also HER-2/neu or ErbB2]). These three are the ones that your oncologist will use to characterize your tumor.

The estrogen and progesterone receptor positive (ER+ and PR+, respectively) tumors are the most common ones. According to WebMD, about 80% of breast cancer tumors are ER+ and 65% are PR+, and these tumors are treated with hormone therapy, generally tamoxifen and aromatase inhibitors (depending on the patient’s menopausal status).

HER2+ is an interesting case. HER2+ tumors contain extra copies of the gene that makes the HER2, which is thought to make cancer cells grow faster. Historically, the prognosis for HER2+ tumors has been worse than for HER2- tumors, with a greater chance of recurrence and metastasis.

At least, that was the case before the development of targeted drugs specifically for HER2, such as trastuzumab (Herceptin), pertuzumab (Perjeta) and others. These drugs don’t come without risks and are known for being potentially cardiotoxic, but they are very effective.

This is the irony. Triple-positive breast cancer went from being one of the more aggressive breast cancers to being almost “curable”. All due to targets.

This is also what makes triple-negative breast cancer (TNBC) more complex. Without specific targets to aim for, treatment of TNBC relies on aggressive chemotherapy, which can be quite effective. But without targeted therapies, TNBC still has the highest rate of recurrence and worst prognosis of all breast cancers. Researchers are furiously searching for new ways to characterize TNBC tumors for this very reason.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

We are all looking forward to the day when we can say there is a definitive cure for cancer.

But what brought on this post? I was searching on the internet for breast cancer info on HER2+ tumors and came across a provocative headline from MedicineNet.com that read, “Can HER2-Positive Breast Cancer Be Cured?” The answer to this, I assumed, would be “no” because we’re not at the point where we can say that we’re definitively “curing” breast cancer.

In addition, I’d been conditioned by my oncologist to think of cancer in terms of years of survival rather than cure.

But according to this MedicineNet article, “With recent advances in medicine, it is considered that HER2-positive breast cancer is curable.” A bold statement indeed. And one that I hope we will be making more and more.

For an article from the American Cancer Society describing available targeted therapies for breast cancer, go here.