Prognosis of Triple-Negative Breast Cancer

How life expectancy and relapse differ from positive tumors

Questions about the survival rate and recurrence rate are very common when someone is diagnosed with triple-negative breast cancer (TNBC). 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 heterogeneous (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.

We will look at factors that may affect survival or recurrence as well as the statistical rates of both. We will also look at life expectancy with stage 4 triple-negative breast cancers and recent case reports of a few long-time survivors.

Triple-Negative Basics

Triple-negative breast cancer 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.

There are fewer options available for treating 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 single 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 different classes; classes that may differ significantly in prognosis.

The definition has also changed, and this can make it difficult to interpret studies. 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

There are a number of factors (in addition to subtypes) that may affect the prognosis of triple negative breast cancer. Some of these include:

Age

In one study, it was 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 follows a different pattern with triple-negative breast cancers than with positive disease.

Early Recurrence

When recurrences occur with triple-negative breast cancer, they commonly occur 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:

Late Recurrence

Triple-negative breast cancers (at least many) differ significantly from hormone-positive tumors in that they are less likely to recur late (defined as 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 5 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 -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 (Life Expectancy With Metastatic TNBC)

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 also 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 five-year overall survival rate was 27%. Post-recurrence survival appears to vary with the site(s) of metastases, with prognosis being better with bone metastases than metastases to other organs. People who have a single metastases also have better survival rates than those who have multiple metastases.

Survival Rates

Many statistics report the overall life expectancy for stage 4 breast cancer (all types) by stage. The American Cancer Society, however, breaks 5-year survival rates down into three categories:

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

These rates were calculated (as of 2019) with statistics gathered between 2010 and 2015.

Are There Long-Term Survivors?

Recent treatments may be changing long-term outlook for at least some people with metastatic triple-negative breast cancer according to two 2019 reports. In one, 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, and as such 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 still 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

The immunotherapy drugs called checkpoint inhibitors have led to a significant improvement in survival rates for lung cancer and melanoma. In March of 2019 the first immunotherapy drug, Tecentriq (atezolizumab) was approved for triple-negative breast cancer that is metastatic (or early-stage but cannot be removed surgically). As noted above, there are at least a few people who have had excellent responses in clinical trials prior to approval.

PARP inhibitors are also a class of medications 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 treating both metastases, and may reduce 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 sometimes 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 heartwrenching 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.

Was this page helpful?

Article Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial policy to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Aysola K, Desai A, Welch C, et al. Triple negative breast cancer - An overviewHereditary Genet. 2013;2013(Suppl 2):001. doi:10.4172/2161-1041.S2-001

  2. Özkurt E, Tükenmez M, Yılmaz R, et al. Favorable long-term outcome in male breast cancerEur J Breast Health. 2018;14(3):180–185. Published 2018 Jul 1. doi:10.5152/ejbh.2018.3946

  3. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer [published correction appears in Arch Pathol Lab Med. 2010 Aug;134(8):1101]. Arch Pathol Lab Med. 2010;134(6):907–922. doi:10.1043/1543-2165-134.6.907

  4. Qiu JD, Xue XY, Li R, et al. Clinicopathological features and prognosis of triple-negative breast cancer: a comparison between younger (<60) and elderly (≥60) patients. European Journal of Cancer Care (England). 2016. 25(6):1065-1075. doi:10.1111/ecc.12346

  5. Stewart RL, Updike KL, Factor RE, et al. A multigene assay determines risk of recurrence in patients with triple-negative breast cancer. Cancer Research. 2019. doi:10.1158/0008-5472.CAN-18-3014

  6. Reddy SM, Barcenas CH, Sinha AK, et al. Long-term survival outcomes of triple-receptor-negative breast cancer survivors who are disease free at 5 years and relationship with low hormone receptor positivity. British Journal of Cancer. 2018. 118(1):17-23. doi:10.1038/bjc.2017.379

  7. Morante Z, De la Cruz Ku GA, Enriquez D, et al. Post-recurrence survival in triple negative breast cancer. Journal of Clinical Oncology. 2018. 36(no. 15_suppl). doi:10.1200/JCO.2018.36.15_suppl.e13120

  8. Pan H, Gray R, Braybrooke, J, et al. 20-Year risks of breast cancer recurrence after stopping endocrine therapy at 5 yearsThe New England Journal of Medicine. 2017;377:1836-1846. doi:10.1056/NEJMoa1701830

  9. American Cancer Society. Triple-negative breast cancer. Updated 09/20/19.

  10. Chue BM, La Course BD. Case report of long-term survival with metastatic triple-negative breast carcinoma: Treatment possibilities for metastatic disease. Medicine (Baltimore). 2019. 98(16):e15302. doi:10.1097/MD.0000000000015302

  11. Chue BM, La Course BD. Can we cure stage IV triple-negative breast carcinoma?: Another case report of long-term survival (7 years). Medicine (Baltimore). 2019. 98(38):e17251. doi:10.1097/MD.0000000000017251

Additional Reading