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What Is Triple Negative Metastatic Breast Cancer

Who Is Most Likely To Have Tnbc

Metastatic Triple-Negative Breast Cancer Ongoing Trials

Triple negative breast cancer appears more frequently in women age 40 and younger than in older women. Black and Latina women are more likely to develop TNBC than white women. Women who have the gene change BRCA1 are more likely to develop TNBC than other women. When the BRCA1 gene mutates, it stops preventing cancer and appears to make your bodys cells more vulnerable to cancer.

Treatments For Metastatic Triple

One myth about treating TNBC is that there arent effective treatment options. The truth is that an array of treatments can improve your care. Your treatment options include many medicines and may also include targeted therapies that treat some triple-negative breast cancers with specific features.

How do you choose from the many available chemotherapy options? It is important to talk with your doctors about how you wish to balance the goals of keeping the cancer under control as long as possible and maintaining your ,or overall enjoyment of life.

Another important point about treating metastatic TNBC is that if you had early- disease, you can retry medicines you were treated with before. A certain treatment may have failed to get rid of the primary disease, but that treatment could still control it in the metastatic setting.

Common chemotherapy treatments for metastatic triple-negative disease are:

  • , which kill cancer cells by stopping growth. Three anthracyclines used in metastatic breast cancer are:

Phase Iii Embrca Trial

In the pivotal phase 3 study EMBRCA, authors investigated talazoparib in 431 patients with gBRCA mutations and MBC. Approximately half of patients had TNBC with the remainder having ER/PR-positive breast cancer. Patients had a median of 2 prior lines of chemotherapy and were randomised in a 2:1 manner to receive talazoparib vs physicians choice . Median PFS was greater in the talazoparib group compared to the control group-8.6 mo vs 5.6 mo with an objective response rate of 62.6% vs 27.2%. Benefit within the TNBC and HR positive subgroups was equivalent. Crucially however, median OS was not significantly greater in the talazoparib group compared to the placebo group . Patients in the talazoparib group did however have improved health related quality of life outcomes. More than a quarter of patients suffered from a grade 3 or grade 4 adverse event in the talazoparib group which was similar to the control group . Notably, one patient suffered from the rare but well described PARPi toxicity of acute myeloid leukaemia.

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Stages Of Breast Cancer

The stage of breast cancer is based on the size and location of the tumor, as well as whether the cancer has spread beyond the part of the breast in which it originated. To determine the stage of breast cancer, healthcare professionals use a scale of stage 0 to stage 4.

Stage 0 breast cancers are isolated in one part of the breast, such as a duct or lobule, and show no sign of spreading into other tissue.

Stage 1 is typically localized, although further local growth or spread may cause the cancer to move into stage 2.

In stage 3, the cancer may be larger and has affected the lymph system. Stage 4 cancer has spread beyond the breast and nearby lymph nodes, and into other organs and tissues of the body.

In addition to stages, breast cancers are given grades based on the size, shape, and activity of the cells in the tumor. A higher-grade cancer means a greater percentage of cells look and act abnormal, or they no longer resemble normal, healthy cells.

On a scale of 1 to 3, with 3 being the most serious, TNBC is often labeled grade 3.

American Cancer Society , the symptoms of TNBC can be the same as those for other types of breast cancer. ACS recommends regular screenings such as mammograms to detect breast cancer before symptoms appear, the time when treatment is most effective.

Other signs of breast cancer include:

Any of these signs can be caused by other conditions. But it is always good to have them checked out by your healthcare professional.

Where Do These Numbers Come From

Metastatic and triple

The American Cancer Society relies on information from the Surveillance, Epidemiology, and End Results Program database, maintained by the National Cancer Institute , to provide survival statistics for different types of cancer.

The SEER database tracks 5-year relative survival rates for breast cancer in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by AJCC TNM stages . Instead, it groups cancers into localized, regional, and distant stages:

  • Localized: There is no sign that the cancer has spread outside of the breast.
  • Regional: The cancer has spread outside the breast to nearby structures or lymph nodes.
  • Distant: The cancer has spread to distant parts of the body such as the lungs, liver, or bones.

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Estrogen And Progesterone Receptor

Estrogen receptor and progesterone receptor are considered the most important prognosis factors even before the invention of hormonal therapy. ER-positive patients with node-negative breast cancer who were treated with local therapy showed higher PFS and OS within 5 years. Hormone receptor is strongly associated with hormonal/endocrine treatment however, hormonal therapy is not useful in hormone receptor negative tumor cases. Moreover, the loss of either PR or ER in recurrent breast cancer will be related with poor response to hormonal/endocrine therapy . Table Table22 shows the percentage distribution of estrogen and progesterone receptors.

Treatment For Triple Negative Breast Cancer

Treatment for triple negative breast cancer usually involves surgery , radiotherapy if breast conserving surgery was performed, and chemotherapy. If you would like to read more about the main types of breast cancer surgery, visit the surgery section of this website.

As triple negative breast cancer is usually very responsive to chemotherapy, your medical oncologist will most likely develop a chemotherapy treatment plan for you. This will take into account your own individual needs and preferences.

Chemotherapy is usually given after breast cancer surgery. Sometimes it is given before surgery to shrink the tumour to allow for a smaller and easier operation. Some people may be offered chemotherapy before surgery this is called neoadjuvant chemotherapy.

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What Is The Treatment For Triple

Chemotherapy.Chemotherapy is almost always called for, Sun says. Chemo can downstage tumors . While Sun says the chemotherapy for triple-negative breast cancer can be intense, she adds that regimen can be tailored to the individual and adjusted for older or frailer patients.

In those cases where we get complete response, we know we gave you the right medicine and your prognosis is good, Sun says.

Surgery can remove more of the tumor. Surgery for triple-negative breast cancer does not always have to be a mastectomy, Sun says. Effective chemotherapy done first opens up the possibility of less-invasive surgical options that are less of an ordeal for the patient. If the tumor is small enough after chemo, outpatient procedures or a lumpectomy may be possible.

Surgical samples of the cancerous tissues taken from surgery can provide more information on the cancer and how it is behaving so chemotherapy can be tailored accordingly.

Radiation therapy involves the use beams of radiation to destroy cancer cells, using various techniques to prevent damage to healthy surrounding tissue.

Medical treatments are being tested on triple-negative breast tumors in clinical trials.

Immunotherapy and PARP inhibitors are very exciting and theres lots of research going on, including here at Johns Hopkins, Sun says.

Treatment Of Stage Iv Breast Cancer

Metastatic Triple-Negative Breast Cancer

Stage IV cancers have spread beyond the breast and nearby lymph nodes to other parts of the body. When breast cancer spreads, it most commonly goes to the bones, liver, and lungs. It may also spread to the brain or other organs.

For women with stage IV breast cancer, systemic drug therapies are the main treatments. These may include:

  • Some combination of these

Surgery and/or radiation therapy may be useful in certain situations .

Treatment can often shrink tumors , improve symptoms, and help some women live longer. These cancers are considered incurable.

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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 became the first immunotherapy drug to be approved for triple-negative breast cancer that is metastatic or locally advanced but unresectable . However, in August 2021, Tecentriq’s manufacturer voluntarily withdrew that indication in the United States.

However, also in 2021, the Food and Drug Administration approved Keytruda for high-risk, early-stage, triple-negative breast cancer. It is used in combination with chemotherapy as a neoadjuvant treatment , and then continued as a single agent as adjuvant treatment .

PARP inhibitors are another class of medication that may alter survival rates in the future, particularly among women who have hereditary breast cancer .

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 , 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.

Data Sources And Software

The PubMed, Cochrane, and Embase databases were searched for eligible studies/publications Microsoft Office Excel was used to synthesize study records. As necessary, trial eligibility criteria were compared against the criteria listed on ClinicalTrials.gov. Meta-analyses of ORR were conducted in R using the metafor package . Qualitative graphical analyses of ORR, DOR, OS, and PFS across identified trials were performed using R .

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What Are Symptoms Of Triple Negative Breast Cancer

TNBC symptoms are the same as other common breast cancers. And many breast cancer symptoms are similar to other less serious conditions. That means having certain symptom doesnt mean you have breast cancer. Possible breast cancer symptoms include:

  • A new lump or mass.
  • Swelling in all or part of a breast.
  • Dimpled skin.
  • Nipple retraction, when your nipple turns inward.
  • Nipple or breast skin thats dry, flaking, thickened or red.
  • Nipple discharge that is not breast milk.
  • Swollen lymph nodes. This symptom happens when breast cancer spreads to the lymph nodes under your arm or near your collarbone.

Pathological And Molecular Characterization Of Triple Negative Breast Cancer

Frontiers

As a distinct molecular entity, TNBCs appear to be quite heterogeneous at a histopathological level. They frequently show features of ductal invasive carcinomas although metaplastic, medullary and apocrine features are also found . Moreover, TNBCs may present themselves as adenoid cystic lesions, histiocytoid carcinomas and even as invasive lobular carcinomas . A relatively large number of breast cancers that do not exhibit a basal phenotype appeared to have a triple-negative profile . Therefore, from a morphological and molecular point of view, TNBC may somehow be classified into four main categories that include the normal-like and the apocrine subtypes . It appears that some histopathological features of breast cancer such as pleomorphic lobular carcinoma and mixed ductal-lobular carcinoma exhibit a triple-negative molecular profile . Also, most invasive carcinomas that develop from microglandular adenosis areas are in fact triple-negative tumors . Recent studies have shown that metaplastic carcinomas are usually TNBCs . Metaplastic carcinomas are known to be rare, aggressive diseases of the breast that are usually diagnosed at grade 3 and, similar to TNBCs, have no specific therapeutic guidelines .

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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 arent 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.

Advanced Cancer That Progresses During Treatment

Treatment for advanced breast cancer can often shrink the cancer or slow its growth , but after a time, it tends to stop working. Further treatment options at this point depend on several factors, including previous treatments, where the cancer is located, a woman’s menopause status, general health, desire to continue getting treatment, and whether the hormone receptor status and HER2 status have changed on the cancer cells.

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What Is The Treatment For Triple Negative Breast Cancer

Healthcare providers and researchers are making significant progress on TNBC treatments. Recent clinical trials are testing new combinations of drugs and new approaches to existing treatments. Some existing treatments are:

  • Chemotherapy: Providers might combine chemotherapy and surgery, with chemotherapy being used to shrink your tumor before surgery or after surgery to kill cancer cells throughout your body.
  • Surgery: This could be a lumpectomy to remove an individual lump, or a mastectomy to remove an entire breast. Providers then perform a sentinel node biopsy or axillary node surgery to look for signs your breast cancer has spread to your lymph nodes.
  • Radiation therapy: Post-surgery radiation therapy helps reduce the chances your cancer will return or recur.
  • Immunotherapy: This treatment stimulates your immune system to produce more cancer-fighting cells or help healthy cells identify and attack cancer cells. Immunotherapy can be added to chemotherapy to before surgery to shrink the tumor. You might also receive immunotherapy for about a year after your surgery and post-surgery radiation therapy.

How Life Expectancy And Relapse Differ From Positive Tumors

2020 PEA Program Metastatic Triple-Negative Breast Cancer Immunotherapy Options & Side Effects

Doru Paul, MD, is triple board-certified in medical oncology, hematology, and internal medicine. He is an associate professor of clinical medicine at Weill Cornell Medical College and attending physician in the Department of Hematology and Oncology at the New York Presbyterian Weill Cornell Medical Center.

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 positive tumors, triple-negative breast cancer is a very diverse disease.

On a positive note, and unlike hormone-positive tumors that commonly recur late , 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.

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Risk Factors For Triple Negative Early Breast Cancer

Anyone can get triple negative breast cancer, however there are some things that increase a persons risk.

Having an inherited BRCA mutation

Everyone has BRCA1 and BRCA2 genes. These genes normally prevent cancers from developing. However if there is a fault, called a mutation, in one of these genes, it can increase a persons risk of developing breast cancer and other cancers including ovarian cancer and prostate cancer in men. These gene mutations can be passed down through families.

About 5-10% of all people diagnosed with breast cancer have an inherited BRCA1 or BRCA2 gene mutation.

A BRCA1 mutation is associated with a higher risk for triple negative breast cancer. Not all breast cancers caused by BRCA mutations are triple negative, however, and not all triple negative breast cancers are caused by inherited BRCA mutations.

BRCA2 mutations are more likely to be present in oestrogen receptor positive breast cancer.

If you have a strong family history of breast and/or ovarian cancer , it is possible that you and your relatives could carry a BRCA mutation. For more information on breast cancer and family history, visit thebreast cancer in the family section of this website.

Being premenopausal

Premenopausal women have a higher rate of triple negative breast cancer than postmenopausal women. Scientists do not yet understand why this is the case, however research is currently underway in this area.

Targeted Therapy In Tnbcs

Different potential therapeutic options in TNBCs are summarized in Figure . Unlike the luminal types and the HER2 overexpressing type of breast carcinomas, TNBC lacks a specific targeted therapy. However, considering TNBCs heterogeneity, it is possible that BRCA1/2 mutations, along with AR may represent potential molecular targets in TNBCs treatment . Also, Pim-2, a serin/threonine kinase strongly involved in breast cancer metastasis, may become a therapeutic target in TNBCs . HJ-PI01, a Pim-2 inhibitor, seems to induce autophagic cell death and apoptosis thus decreasing malignant proliferation in TNBC cell lines . Shindikar et al. highlighted the anticancer properties of curcumin and resveratrol in TNBCs treatment, however, difficulties regarding their in vivo availability, distribution and kinetics along with a poor solubility, limits their routine use in patients . Chemotherapeutic agents such as nab-paclitaxel seems to be beneficial in the treatment of aggressive forms of breast cancer, such as TNBCs and HER2+, as well as in elderly and taxane-pretreated women .

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Types Of Breast Cancer

There are several types of breast cancer, and any of them can metastasize. Most breast cancers start in the ducts or lobules and are called ductal carcinomas or lobular carcinomas:

  • Ductal carcinoma. These cancers start in the cells lining the milk ducts and make up the majority of breast cancers.
  • Lobular carcinoma. This is cancer that starts in the lobules, which are the small, tube-like structures that contain milk glands.

Less common types of breast cancer include:

  • Medullary

  • Metaplastic

  • Papillary

  • Inflammatory breast cancer is a faster-growing type of cancer that accounts for about 1% to 5% of all breast cancers.

  • Pagets disease is a type of cancer that begins in the ducts of the nipple.

Breast cancer can develop in women and men. However, breast cancer in men is rare. Less than 1% of all breast cancers develop in men.

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