Triple negative breast cancer - information pack

Also known as:

  • TNBC
  • ER/PR negative
  • HER2 negative breast cancer

Classification Code ICD-10-CM C50


How rare is triple negative breast cancer?

In the UK and Europe the usual definition of a rare cancer is one that occurs in less than 6 people out of every 100,00 each year. Because there are around 200 rare cancers, this means that they make up about 24% (nearly a quarter) of all cancers.

Triple negative breast cancer occurs in around 13 people per 100,000 but only makes up around 1 in 5 (20%) of all breast cancers, so it is considered to be rare.

What is triple negative breast cancer?

A short summary:

In short, it is a relatively aggressive breast cancer that is not affected by hormones in the same way as more common forms of breast cancer.  It is also more common in younger patients and those with African ancestry.

In more detail:

Breast cancer is a cancer that has formed in any of the tissues of the breast. The most common place is the lining of the milk ducts, although it can also form in the milk producing glands (lobules).

Most breast cancers have at least one of three features that allow them to grow in response to particular hormones. These hormones are the “female” hormones oestrogen and progesterone and a third called human epidermal growth factor (HER for short).

For a hormone to make a cell divide it has to stick or “bind” to the surface of the cell and the cell recognises this and a message gets sent to start the process of making more cells. This binding process isn’t random. The surface of cells aren’t smooth – they’re covered in lots of different molecules with different shapes and sizes, a bit like an ice lolly covered in sprinkles.

A hormone like oestrogen can only bind to a cell if there is a molecule the right shape to fit it. These molecules are called receptors.

As part of the diagnosis, the cancer tissue from either a biopsy or surgery will be tested to see if it has receptors for these three hormones. If they are missing they are called oestrogen receptor negative, progesterone receptor negative or HER2 negative. If all three are absent then it is called “triple negative” or sometimes TNBC for short.

Triple negative breast cancers are cancers whose cells don’t have receptors for:

  • the hormone oestrogen
  • the hormone progesterone
  • a protein called Her2

Several treatments for common breast cancers work in part by stopping hormones binding to the cell receptors and making the cancer grow. Well known medicines such as Herceptin and Tamoxifen work this way. If your cancer is triple negative these drugs will have no effect on your cancer because they are not affected by the hormones.

Risk factors

We can’t say for certain exactly what caused most cancers. There is a long list of risk factors for all breast cancers that increase the chances of developing it e.g. being overweight, drinking alcohol, physical activity, age but they’re not a guarantee. You may have many risk factors, yet not develop cancer, or you may have none and still develop breast cancer. Scientists are still discovering exactly how risk factors lead to cancer.

Some risk factors are particularly associated with triple negative breast cancer.

A few breast cancers (about 2 in 100), are caused by errors in genes called BRCA1 and BRCA 2. These genes normally help repair damage to your DNA that can cause cancer, so if they are faulty you are more at risk of getting cancer. Triple negative cancers, especially a rare basal cell type, are more likely to have a fault with BRCA1. For women with breast cancer and the BRCA1 gene mutation 75% are likely to be triple negative, although we don’t yet know why this is. The BRCA1 mutation can be inherited.

Another risk is being younger – TNBC is more common than other breast cancers if you are premenopausal. Another risk factor that is not well understood is ethnicity – up to 40% of african-american women with breast cancer will be triple negative.

Some men have triple negative breast cancer but this is very rare. Most men have oestrogen receptors in their cancer cells.

Breast cancer receptors and treatment

Several treatments for common breast cancers work in part by stopping hormones binding to the cell receptors and making the cancer grow. Well known medicines such as the targeted cancer drug trastuzumab (Herceptin™) and Tamoxifen work this way. If your cancer is triple negative these drugs will have no effect on your cancer because they are not affected by the hormones.

This doesn’t mean that TNBC can’t be treated, instead a combination of other drugs, surgery and radiotherapy will be used.

As TNBC is an aggressive cancer, growing more quickly, more likely to spread and more likely to return, the survival rate is lower than for hormone responsive breast cancers. This depends on how far the disease has progressed when it is diagnosed, but the 5 year survival is typically 77% compared to 85% for other types of breast cancer, with the best recovery being associated with early diagnosis and no distant spread (“metastasis”).

What are the current treatment options?

Treatments are adjusted to take account the size of the tumour and whether it has spread (the “stage”) and its appearance under the microscope (its grade) as well as the position of the tumour in the breast and the general health of the patient.

Surgery and radiotherapy

These are the usual types of treatment for most patients. The extent of surgery may vary from removal of the entire breast (mastectomy) to more conservative, breast conserving, operations. The procedure usually involves removal of lymph nodes to check for spread.

Breast conserving operations are usually followed by radiotherapy to the remaining breast tissue. For more information on radiotherapy see the RareCan article.


Chemotherapy may be used before surgery (sometimes called “adjuvant therapy” – adjuvant means to “make stronger”) to reduce tumour size and is common after surgery to reduce the risk of the cancer returning. Treatment may involve combinations of drugs such as

  • doxorubicin
  • epirubicin
  • paclitaxel
  • docetaxel
  • carboplatin
  • cisplatin


These are frequently associated with significant side effects (toxicity) as they generally affect all dividing cells in your body.

This section explains in some detail how the main chemotherapy drugs work.

When any cell divides all of the genetic information it contains in the form of the DNA has to be copied and shared exactly equally between the two new cells. This is a very complex process which also makes it a great target for drugs that can stop it happening effectively.

Doxorubicin is a type of chemotherapy drug called an anthracycline. It slows or stops the growth of cancer cells by blocking an enzyme called topo isomerase 2. This makes it harder for them to divide.

Epirubicin is also an anthracycline. It has a slightly different action to doxorubicin but like doxorubicin damages the DNA in cancer (and normal) cells, stopping them from dividing and growing.

Paclitaxel and docetaxel both act by blocking the formation of structures called microtubules in cancer cells. When cells divide, the DNA is packaged into chromosomes, the X-shaped structures that you often see when people talk about DNA. These chromosomes are the cells “suitcases” for moving DNA around. Microtubules are needed to move DNA into two groups when cells divide. So these drugs stop the separation of chromosomes during cell division which means the division fails and the cells die.

Carboplatin and cisplatin are both “alkylating agents”. They work by binding to DNA and interfering with cell division by stopping the DNA from being copied.

What are the current clinical trials for TNBC?

23 studies recruiting in the UK were listed on in November 2022

The notes on these studies include a lot of specialised language. If you are asked to be involved in one of the clinical trials your medical team will explain the science to you if you want to know more.

ADCT-301 (camidanlumab tesirine, Cami) is an antibody-drug conjugate composed of a monoclonal antibody that binds to CD25 (HuMax®-TAC, licensed from Genmab A/S), conjugated to a toxin (pyrrolobenzodiazepine, PBD) . Once bound to a CD25-expressing cell, Cami is internalized into the cell where enzymes release the PBD-based warhead. In addition to CD25-expressing tumor cells, Cami depletes CD25-positive immune cells in the local tumor environment, which enhances immune-mediated anti-tumor activity.

Pembrolizumab works by inhibiting lymphocytes’ PD-1 receptors, blocking the ligands that would deactivate it and prevent an immune response. This allows the immune system to target and destroy cancer cells, but also blocks a key mechanism preventing the immune system from attacking the body itself.

Dato-DXd (Datopotamab deruxtecan) is an antibody-drug conjugate consisting of a humanized anti-TROP2 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker.

Capivasertib (AZD5363) is a novel, selective ATP-competitive pan-AKT kinase inhibitor that exerts similar activity against the three AKT isoforms, AKT1, AKT2, and AKT3

BT8009 is a Nectin-4 targeting Bicycle toxin conjugate. Bicycle toxin conjugates (BTCs) are a new class of anticancer agents that allow efficient and targeted delivery of toxin payloads into tumours. Nectin-4 is overexpressed in multiple tumour types and is a clinically validated target for selective delivery of cytotoxic payloads.

Nivolumab targets PD-1

BT5528, a BTC targeting EphA2

Olaparib inhibits poly(ADP‐ribose) polymerase, thereby blocking the repair of single‐strand DNA breaks. This results in synthetic lethality in BRCA‐associated cancer cells, which have a dysfunction of another DNA repair pathway – homologous recombination.

TT-702 is a ‘small molecule prodrug’. TT-702 is converted into TT-478, which then targets and blocks the function of the ‘A2B adenosine receptor’. Adenosine signaling via the A2A and A2B receptors is emerging as an important regulatory mechanism of immune responses

Magrolimab, a humanised monoclonal antibody targeting the human cell surface antigen CD47, with potential immunostimulating and antineoplastic activities.

Sacituzumab govitecan is an ADC that consists of a humanised antibody that recognizes Trop-2 covalently attached to the topoisomerase I inhibitor SN-38. The ADC binds to Trop-2–expressing cancer cells, releasing the cytotoxic SN-38.

Niraparib inhibits the role of PARP enzymes, PARP-1 and PARP-2, in DNA repair. By blocking PARP enzymatic activity and increasing the formation of PARP–DNA complexes, niraparib induces DNA damage and cell death.

Atezolizumab is a humanised monoclonal antibody immune checkpoint inhibitor that selectively binds to PD-L1 to stop the interaction between PD-1 and B7. 1 (ie, CD80 receptors). The antibody still allows interaction between PD-L2 and PD-1

Capecitabine is a prodrug that is enzymatically converted to fluorouracil (antimetabolite) in the tumour, where it inhibits DNA synthesis and slows growth of tumour tissue.

Ipatasertib binds to and inhibits the activity of Akt in a non-ATP-competitive manner, which may result in the inhibition of the PI3K/Akt signalling pathway and tumour cell proliferation and the induction of tumour cell apoptosis

SGN-LIV1A targets the zinc transporter LIV-1, expressed by oestrogen receptor-positive breast cancers

Bevacizumab acts by selectively binding circulating VEGF, thereby inhibiting the binding of VEGF to its cell surface receptors. This inhibition leads to a reduction in microvascular growth of tumour blood vessels and thus limits the blood supply to tumour tissues.

Gemcitabine is a nucleoside analog that mediates its antitumour effects by promoting apoptosis of malignant cells undergoing DNA synthesis.

Eribulin is a novel microtubule inhibitor with mitotic and nonmitotic mechanisms of action.

Tocilizumab is a novel monoclonal antibody that competitively inhibits the binding of interleukin-6 (IL-6) to its receptor (IL-6R)

Selicrelumab binds to CD40 on a variety of immune cell types. This triggers the cellular proliferation and activation of antigen-presenting cells (APCs), and activates B cells and T cells, resulting in an enhanced immune response.

INCB106385 is a potent, selective and orally bioavailable dual antagonist of A2A and A2B receptors.

INCMGA00012 is a humanized immunoglobulin G4 (IgG4) monoclonal antibody against human PD-1

ASTX660 (Tolinapant) is an antagonist of the cellular and X-linked inhibitors of apoptosis proteins (cIAP1/2 and XIAP). Inhibitors of apoptosis proteins (IAPs) are frequently overexpressed in tumour cells and contribute to tumour cell survival and chemo-resistance. By inhibiting IAPs, tolinapant promotes cell death.

AZD6738 is an inhibitor of the Serine/Threonine protein kinase Ataxia Telangiectasia and Rad3 related (ATR)

Durvalumab is a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80 (B7. 1) to release the inhibition of immune responses, without inducing antibody-dependent cell-mediated cytotoxicity

KY1044, is a fully human IgG1 anti ICOS antibody designed to stimulate Teffs and to deplete ICOS high Tregs in the tumour microenvironment.

Alpelisib selectively inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signalling pathway, thereby inhibiting the activation of the PI3K signalling pathway.

NX-1607 is an inhibitor of Casitas B-lineage lymphoma proto-oncogene B (CBL-B)

Palbociclib inhibits the phosphorylation of retinoblastoma (Rb) protein, through inhibition of cyclin D-CDK4/6 complex activity, blocking cell cycle progression from G1 into S phase.

Avelumab binds to programmed cell death 1 protein (PD-1) and controls PD-L1 interactions. It also enables the activation of T-cells and the adaptive immune system

Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur d’Origine Nantais (RON)

Fulvestrant is an anti-estrogen

Modi-1 is a vaccine composed of a combination of three peptides from two target antigens that are commonly modified in cancer cells.

SEA-TGT is an enhanced human mAb that targets TIGIT and blocks TIGIT’s interaction with CD155 and CD112. T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor expressed on subsets of T cells and NK cells.

Sasanlimab, a monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2

Key researchers (UK and international)




Prof Andrew Tutt

Head of Breast Cancer Now Research Unit

King’s College London

Where can I find support groups?




UK Charity for triple negative breast cancer

A new charity following the TNBC foundation model

TNBC Foundation (US)

A new charity following the TNBC foundation model

Breast Cancer Now

An excellent source of information on the latest research as well as support for patients

Incidence data for triple negative breast cancer

Table of Incidence Data (may not be complete)

RareCare list

Other estimates

Links to alternative data source

Incidence (per 100,000)


UK incidence (per annum)

8,250 (15% of total of 55,000)

UK prevalance

Europe prevalance

US prevalance*

*estimate based on assumption that US population is ~5x UK


Age range affected

More common under 40

Gender balance

Predominantly women but does occur in men

Ethnicity data

More common in black women

Incidence data may not be complete.

Incidence per 100,000 – 12

UK incidence per 100,000 – 

UK Prevalance – 

Europe prevalance – 

US prevalance (estimate based on assumption of ~5x UK population) – 

Link to alternative data source – Cancer Research UK

Age range affected – more common under 40

Gender balance – predominantly women but does occur in men

Ethnicity data – more common in black women (