Triple Negative Breast Cancer Not Responding to Chemo

Without specific hormone receptors, these aggressive tumors are harder to treat

Triple-negative breast cancer (TNBC) is difficult to treat due to its aggressive nature. It often responds initially to chemotherapy but is the most common breast cancer to recur; when it recurs, it is more resistant to chemotherapy, making it less responsive and more challenging to treat.

This article discusses current research for new TNBC medications, options for unresponsive TNBC, alternative and complementary therapies to help with treatments' side effects, and where to find support.

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TNBC Prevalence

It is estimated that triple-negative breast cancer accounts for 15–20% of all breast cancers. It tends to occur more often in young women, people with an inherited BRCA1 gene mutation, and Black, non-Hispanic Black, and African American women.

The Missing Link in TNBC and Chemo Research

Cytotoxic (cancer-cell-killing) chemotherapy has been the primary treatment therapy for triple-negative breast cancer. Doses are often high, given triple-negative breast cancer's aggressive nature.

In the past decade, scientists have searched for alternative treatment options that require lower doses and minimize chemotherapy's side effects.

Combination therapy (chemotherapy with a non-chemotherapy medication) is one potential option scientists are exploring. With this treatment, the chemotherapeutic medications will kill the cancer cells, while non-chemotherapy medicines, such as a drug-inhibited tumor-associated macrophage, will block the body's immune response against the tumor; together, they will effectively destroy the cancer cells.

Research indicates the two-step approach may effectively treat highly aggressive triple-negative breast cancer tumors and prevent metastasis (cancer spread).

Some of the alternative options that still need further evaluation include the following:

  • Use of third-generation chemotherapy medications (a newer class of agents)
  • Use of metronomic polychemotherapy (continuous, daily, or weekly low-dose drugs administered for a longer time)
  • Platinum chemotherapy medications interfere with the deoxyribonucleic acid (DNA) responsible for cellular activity, preventing cancer cell growth

Treatment Options for Unresponsive TNBC After Chemo

TNBC is an aggressive form of breast cancer with limited treatment options. Because triple-negative breast cancer does not respond to hormonal therapy or other medicines that target the HER2 gene, chemotherapy is the most frequent treatment option.

However, given TNBC's aggressiveness and resistance to treatment options, finding additional treatment options to target the cancer is critical to long-term treatment success. There are two relatively recent treatment options now available:

  • Trodelvy (sacituzumab govitecan-hziy): Trodelvy received accelerated U.S. Food and Drug Administration (FDA) approval as a targeted therapy specifically for triple-negative breast cancer. Trodelvy targets a specific cancer cell receptor that prevents cancer growth and spread.
  • Keytruda (pembrolizumab): Keytruda received FDA approval to treat triple-negative breast cancer that cannot be surgically removed or has grown beyond the initial site of the cancer tumor.


If triple-negative breast cancer has been successfully treated but comes back, it is considered recurrent. Treatment options for recurrent TNBC include:

  • Surgical removal of the breast cancer
  • Chemotherapy in combination with an antibody-drug conjugate, such as sacituzumab govitecan-hziy
  • Participation in various clinical trials for newer TNBC therapies


Metastatic cancer has spread elsewhere from the initial breast cancer site. Treatment for triple-negative breast cancer is more complex when the cancer metastasizes. In addition to standard chemotherapy medications, treatment considerations for metastatic TNBC include:

  • Adding platinum chemotherapy medications, such as Platinol, Platinol-AQ (cisplatin), or Paraplatin (carboplatin)
  • Poly (ADP-ribose) polymerase inhibitors, such as Lynparza (olaparib) or Talzenna (talazoparib), which prevent cancer cells damaged by chemotherapy from repairing themselves. The tumors of people with triple-negative breast cancer may carry BRCA1 or BRCA2 mutations and Lyparza or Talzenna are particularly useful in this situation.
  • An immunotherapy, like pembrolizumab, if the TNBC cells have a specific type of protein that's susceptible to it

CAM Therapies

Complementary and alternative medicine (CAM) do not cure triple-negative breast cancer. Still, they can help people affected by TNBC find relief from treatment side effects, such as nausea, pain, or fatigue.

Discussing CAM therapies with your healthcare provider to ensure their inclusion won't adversely affect your current treatment plan is essential. CAM therapies include:

  • Mind-body therapies: These therapies combine internal focus, breathing, and body movements to relax the body and mind. Some examples include meditation, biofeedback, hypnosis, yoga, tai chi, and visual imagery.
  • Biologically based practices: Biologically based practices use elements of nature. This includes vitamins, dietary supplements, botanicals, spices (like turmeric), plants (like cannabis), and special foods or diets.
  • Manipulative and body-based practices: This includes massage therapy or reflexology.
  • Energy healing: This type of healing focuses on balancing your internal energy flow. Examples of energy healing include reiki and therapeutic touch.
  • Whole medical systems: Whole medical systems are based on healing beliefs from other cultures and parts of the world and are not typically found within traditional Western medicine. These include Ayurvedic medicine, traditional Chinese medicine, and naturopathic medicine.

Emotional and Physical Burden of Unresponsive TNBC

Triple-negative breast cancer treatment can cause a multitude of physical symptoms, including:

  • Nausea
  • Hair loss
  • Fatigue
  • Swollen lymph nodes

Cancer can also affect your emotional health in various ways. Feelings might change from moment to moment and get intense at times. It is entirely normal to have a wide range of emotions, including:

  • Feeling overwhelmed
  • Anger
  • Fear and worry
  • Hope
  • Gratitude
  • Stress and anxiety
  • Sadness or depression
  • Guilt
  • Loneliness

Some suggested ways to cope with these emotions include the following:

  • Express your feelings
  • Don't blame yourself for your cancer
  • Don't pretend to be happy or positive when you are not
  • Find support to work through your emotions
  • Identify what you can control, such as activity level or diet choices

Where to Find TNBC Support

There are several organizations dedicated to supporting people diagnosed with breast cancer. The following organizations offer support, access to prevention and screening, recommendations to find appropriate healthcare professionals, and much more:


Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancers and is considered the most aggressive form of breast cancer. Triple-negative breast cancer lacks certain receptors (estrogen, progesterone, and HER2), meaning treatment is usually limited to chemotherapy.

Although triple-negative breast cancer initially responds well to chemotherapy, it is more likely to recur and come back more resistant to treatment. Researchers continue to study new medication options, including combination therapy. Side effects from chemotherapy are often present, but complementary and alternative therapy options may help address symptoms.

TNBC can cause many physical and emotional challenges, so understanding where to find support and resources is essential to your overall health and recovery.

Frequently Asked Questions

  • What is the survival rate of triple negative breast cancer?

    Survival rates are based on the type and stage of cancer. For triple-negative breast cancer staged as localized at the time of diagnosis, the five-year survival rate is 91%. In comparison, a triple-negative breast cancer staged as metastasized, distant from the location of the triple-negative breast cancer, has a 12% five-year survival rate. In total, triple-negative breast cancer has a 77% five-year survival rate.

  • How often does triple negative breast cancer return?

    Relapse rates can vary based on the initial staging of the triple-negative breast cancer and the initial response to treatments. Generally, triple-negative breast cancer has the highest recurrence rate at around 17%.

  • Do triple negative breast cancer cells spread during chemotherapy?

    Though rare, some evidence indicates that cancer cells can spread during chemotherapy. Working with a healthcare provider, such as an oncologist, to properly determine the presence of triple-negative breast cancer and select the most appropriate chemotherapy regimen is essential to prevent chemotherapy-induced metastasis (spreading).

12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Pamela Assid, DNP, RN
Pamela Assid, DNP, RN, is a board-certified nursing specialist with over 25 years of expertise in emergency, pediatric, and leadership roles.