Is stage 4 triple negative breast cancer curable

Questions about the survival rate and recurrence rate are very common when someone is diagnosed with triple-negative breast cancer. While prognosis is, on average, poorer than with hormone receptor or human epidermal growth factor receptor 2 (HER2) positive tumors, triple-negative breast cancer is a very diverse disease.

On a positive note, and unlike hormone-positive tumors that commonly recur late (after five years), late recurrence is less common with triple-negative tumors. The recent approval of immunotherapy only for triple-negative disease is also optimistic.

This article looks at factors that may affect survival or recurrence of triple-negative breast cancer, as well as the statistical rates of both. It also discusses life expectancy with stage 4 and recent case reports of some longtime survivors.

Triple-Negative Basics

Triple-negative breast cancers are cancers that don’t express estrogen or progesterone receptors and also lack overexpression of HER2. Roughly 10% to 20% of breast tumors are triple-negative at the time of diagnosis.

These tumors are more common in women who have BRCA mutations (especially BRCA1), as well as some non-BRCA gene mutations associated with breast cancer. They are very uncommon in men, with only around 1% of breast cancers in males being triple-negative.

Fewer treatment options are available for triple-negative breast cancer, since hormonal therapies (such as tamoxifen or aromatase inhibitors) and HER2-targeted therapies (such as Herceptin) are ineffective. That said, triple-negative tumors tend to respond better to chemotherapy.

For metastatic triple-negative tumors, an immunotherapy drug was approved in 2018 only for triple-negative breast cancer.

In the first years following a diagnosis, the survival rates for triple-negative breast cancers are lower, but unlike estrogen-positive tumors that are notorious for having late recurrences, triple-negative tumors are much less likely to recur after five years.

What this means is that while triple-negative breast cancer may be less “treatable,” it may be more “curable” (or at least lead to long-term survival) among those who survive at least five years.

Not All Triple-Negative Breast Cancers Are the Same

Before discussing statistics, it’s important to note that every person and every tumor is different. Two stage 2A triple-negative breast cancers may behave very differently.

While a discussion is beyond the scope of this article, researchers have been attempting to classify triple-negative tumors into classes, each of which may differ significantly in prognosis.

In the past, triple-negative breast cancers included tumors that had estrogen receptor (ER) or progesterone receptor (PR) expression less than 10%. In 2010, the American Society of Clinical Oncology redefined the criteria to an ER and PR expression less than 1%.

Factors That May Affect Prognosis

A number of factors (in addition to subtypes) may affect the prognosis of triple-negative breast cancer. These include age and treatment type.

Age

One study found that the five-year disease-free and overall survival were significantly higher in older people with triple-negative breast cancer than younger people, even though the older people were less likely to receive treatment with radiation and chemotherapy.

Treatments

Triple-negative breast cancers tend to respond well to chemotherapy—even better than hormone-positive tumors.

Adjuvant chemotherapy (chemotherapy given after surgery) is associated with better survival, and this appears to be true even for small, node-negative tumors. The advantage of chemotherapy varies with tumor grade, with the benefit of chemotherapy most apparent with grade 3 tumors.

Since the majority of stage 4 (metastatic) breast cancers are initially diagnosed at an early stage but later recur with distant metastases, it’s helpful to begin by discussing recurrence rates.

Recurrence Rates

Even with surgery (and often chemotherapy and radiation), breast cancers recur far too commonly. In fact, the majority of stage 4 (metastatic) breast cancers were initially diagnosed at an early stage and later recurred with distant metastases.

Since metastases are responsible for roughly 90% of breast cancer-related deaths, significant research is looking at ways to reduce recurrence risk.

According to a 2019 study, around 40% of people who have stage 1 to stage 3 triple-negative breast cancer will have a recurrence following standard treatment, while around 60% will have long-term disease-free survival.

Unfortunately, there hasn’t been a clear way to determine the chances that a person’s triple-negative breast cancer will recur, and research is in progress.

Both the incidence and timing of recurrence follow a different pattern with triple-negative breast cancers than with positive disease.

Early Recurrence

When recurrences do occur with triple-negative breast cancer, they commonly happen in the first five years after diagnosis. The peak incidence is at roughly three years out from diagnosis.

As with hormone- or HER2-positive breast cancers, recurrences may be local, regional, or distant (metastatic). Yet the sites of distant metastases are often different.

Triple-negative breast cancers are more likely to spread to “visceral organs” such as the brain, liver, and lungs, and unlike estrogen-positive tumors, are less likely to spread to bones.

In a 2018 study, the first site of metastasis was as follows:

• Lung (31%)
• Brain (17.1%)
• Bone (9%)
• Liver (6.2%)
• Leptomeningeal (1.4%)
• Others (7.1%)

Late Recurrence

Many triple-negative breast cancers differ significantly from hormone-positive tumors in that they are less likely to recur late, that is, five or more years following diagnosis.

With estrogen-receptor-positive tumors, the incidence of recurrence remains steady for at least 20 years following the diagnosis, even for very small, early-stage tumors. In fact, people who have estrogen-receptor-positive early-stage breast cancer are more likely to have a recurrence after five years than in the first five years following diagnosis.

In women with hormone-positive tumors who are treated with hormonal therapy for five years after surgery and/or radiation/chemotherapy, the distant recurrence rate between year five and year 20 ranges from 14% for small, node-negative tumors (T1N0) to 47% for larger tumors that have spread to lymph nodes (T2N4-9).

The lower incidence of late recurrence with triple-negative breast cancer wasn’t as clear until recently, as many studies only went out five years when looking at recurrence and survival.

A 2018 study, however, looked at people with triple-negative breast cancer who were disease-free five years after their diagnosis. Among this group, the 10-year recurrence-free rate was 97% and the 15-year recurrence-free rate was 95%.

Since this study began before the definition of triple-negative breast cancer changed, it included people with low estrogen-positive tumors (1% to 10%). Overall, only 5% of the people who survived for five years following their diagnosis had a recurrence.

The reasons for these differences between hormone-positive and hormone-negative tumors aren’t certain, but “tumor dormancy” or the ability for cancer cells to lie dormant for extended periods of time appears to be greater in estrogen-positive tumors.

Post-Recurrence Survival

If you have stage 4 triple-negative breast cancer, you may wonder how long people can live with the disease. Unfortunately, survival rates following a distant recurrence of triple-negative breast cancer are lower than with positive tumors. With that said, survival rates are statistics and do not account for new treatments that have been released in the past few years.

A 2018 study specifically addressed post-recurrence survival in people with triple-negative breast cancer. The overall three-year survival rate was 44% and the overall five-year survival rate was 27%.

Post-recurrence survival appears to vary with the sites of metastases, with prognosis being better with bone metastases than metastases to other organs. People who have a single metastasis also have better survival rates than those who have multiple metastases.

Survival Rates

The American Cancer Society breaks five-year survival rates down into three categories:

• Local (91%)
• Regional (65%)
• Distant (11%)

Are There Long-Term Survivors?

Recent treatments may be changing the long-term outlook for at least some people with metastatic triple-negative breast cancer, according to two 2019 reports.

In one report, a woman is currently 15 years out from her diagnosis of stage 4 triple-negative breast cancer without any evidence of disease. She received both metronomic chemotherapy and immunotherapy.

In another report, a woman achieved a complete response to treatment (also chemotherapy and immunotherapy) and is seven years out from her diagnosis of metastatic disease without evidence of recurrence.

A Note About Statistics

Survival rates are statistics. As such, they tend to tell us how the “average” person will do with an “average” triple-negative breast cancer. But people and tumors aren’t statistics. Some people will do better, and some people will do worse.

Very importantly, statistics are usually several years old. In order to calculate five-year survival rates, a person would have to have been diagnosed at least five years prior, and there is lag time. The treatment of triple-negative breast cancer is changing, and new drugs have been approved.

New Medications for Metastatic Breast Cancer

Immunotherapy drugs called checkpoint inhibitors have led to a significant improvement in survival rates for lung cancer and melanoma.

In 2019, Tecentriq (atezolizumab) became the first immunotherapy drug to be approved for triple-negative breast cancer that is metastatic or locally advanced but unresectable (this means it cannot be removed surgically). However, in August 2021, Tecentriq's manufacturer voluntarily withdrew that indication in the United States.

However, also in 2021, the Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) for high-risk, early-stage, triple-negative breast cancer. It is used in combination with chemotherapy as a neoadjuvant treatment (delivered before the main treatment, usually surgery, to shrink tumor size), and then continued as a single agent as adjuvant treatment (after surgery).

PARP inhibitors are another class of medication that may alter survival rates in the future, particularly among women who have hereditary breast cancer (both BRCA and non-BRCA mutations).

For bone metastases, bone-modifying drugs may be effective in both treating metastases and possibly reducing the development of further metastases in bone.

Finally, for people who have only a single or a few metastases (oligometastases), treating these metastases locally may be an option. While studies are young, treating oligometastases may improve survival or even lead to long-term survival for a minority of people.

In addition, for some people treated with immunotherapy, local radiation (such as stereotactic radiotherapy/cyberknife) may improve the response of immunotherapy, something known as the abscopal effect. Since immunotherapy is such a recent addition to breast cancer, it’s not known how common this response may be or if it will be seen at all.

Statistics Don’t Account for Late Recurrences

When comparing triple-negative breast cancer to positive tumors, it’s important to keep in mind late recurrences. Most statistics are presented as five-year survival rate, and in this setting, triple-negative breast cancer can look more ominous. But looking at longer periods of time, say 20 years following diagnosis, this may be different.

A Word From Verywell

It can be heart-wrenching to be diagnosed with a disease that is associated with a poor prognosis. We can’t disregard the threat of early recurrences, and better treatments are needed.

For those who survive the first five years following their diagnosis, however, a diagnosis of triple-negative disease may lessen the fear of recurrence, at least to a small degree.