What is TNBC

Diagnosis

The diagnosis of a triple negative breast cancer is usually simple. It all starts when a man or a woman feels a lump in the breast. Sometimes it’s the gynecologist or primary care physician that finds it on a routine exam. Other times, the lump can’t be felt at all and is seen on a mammogram or ultrasound (sonogram). Once it is detected by any means, the patient is referred to a breast surgeon for evaluation and a biopsy will be performed. The biopsy should always be a, “minimally invasive biopsy” as opposed to taking the patient to the operating room and removing it surgically. There are three types of minimally invasive biopsies:

The diagnosis of a triple negative breast cancer is usually simple. It all starts when a man or a woman feels a lump in the breast. Sometimes it’s the gynecologist or primary care physician that finds it on a routine exam. Other times, the lump can’t be felt at all and is seen on a mammogram or ultrasound (sonogram). Once it is detected by any means, the patient is referred to a breast surgeon for evaluation and a biopsy will be performed. The biopsy should always be a, “minimally invasive biopsy” as opposed to taking the patient to the operating room and removing it surgically. There are three types of minimally invasive biopsies:

 

  1. Ultrasound guided core biopsies where the biopsy device is directed into the tumor by using an ultrasound machine.
  2. Stereotactic vacuum assisted core biopsies where the biopsy device is directed into the tumor with the aid of a mammogram.
  3. MRI guided vacuum assisted core biopsies where it is the MRI machine that directs the biopsy device. The idea is to remove a few cores of tumor for pathologic analysis regardless of which device is used. After the biopsy a small clip about the size of a pin head is placed in the center of the tumor. This will help identify the location of the tumor in the future. The small samples of tumor are sent to the pathology lab where the diagnosis of a triple negative breast cancer is established. These biopsies are performed as an outpatient under local anesthesia and with little pain.
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The diagnosis of a triple negative breast cancer is usually simple. It all starts when a man or a woman feels a lump in the breast. Sometimes it’s the gynecologist or primary care physician that finds it on a routine exam. Other times, the lump can’t be felt at all and is seen on a mammogram or ultrasound (sonogram). Sometimes the cancer is found by advanced breast imaging techniques such as breast MRI or contrast enhanced mammography (CEM).

Once it is detected by any means, the patient is referred to a breast surgeon for evaluation and a biopsy will be performed. The biopsy should always be a, “minimally invasive biopsy” as opposed to taking the patient to the operating room and removing it surgically. There are three types of minimally invasive biopsies:

  1. Ultrasound guided core biopsies where the biopsy device is directed into the tumor by using an ultrasound machine.
  2. Stereotactic vacuum assisted core biopsies where the biopsy device is directed into the tumor with the aid of a mammogram.
  3. MRI guided vacuum assisted core biopsies where it is the MRI machine that directs the biopsy device. The idea is to remove a few cores of tumor for pathologic analysis regardless of which device is used. After the biopsy a small clip about the size of a pin head is placed in the center of the tumor. This will help identify the location of the tumor in the future. The small samples of tumor are sent to the pathology lab where the diagnosis of a triple negative breast cancer is established. These biopsies are performed as an outpatient under local anesthesia and with little pain.
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Pathology

Estrogen and Progesterone receptors are normal proteins that exist on the surface of all breast cells. Some breast cancers maintain their ability to make the receptors and some cancers loose that ability. If the cancer does not express those receptors on the surface of its cells and has therefore lost the ability to make those receptors it is Estrogen and Progesterone receptor negative (ER, PR negative).

Estrogen and Progesterone receptors are normal molecules that exist on the surface of normal breast cells. Some breast cancers maintain their ability to make the receptors and some cancers loose that ability. If the cancer does not express those receptors on the surface of its cells and has therefore lost the ability to make those receptors it is Estrogen and Progesterone receptor negative (ER, PR negative). The her2/neu oncogene is a normal gene that all people have. Some cancers make multiple copies of the gene and are therefore considered to, "overexpress" this gene and are called her2/neu positive cancers while other cancers that have a normal number of copies and are called her2/neu negative. A cancer with a normal her2/neu profile (her2/neu negative) that is also Estrogen and Progesterone negative (ER, PR negative) is a triple negative cancer. 

One other aspect that is evaluated pathologically is what is called the differentiation of the tumor. If the microscopic characteristics of the cancer are very similar to normal breast tissue then those cancers are considered to be well differentiated. Conversely, if the pathologic characteristics are completely different then the pathologic characteristics of normal breast tissue that tumor is considered to be poorly differentiated. A large proportion of triple negative breast cancers are poorly differentiated and therefore exhibit a more aggressive behavior then well-differentiated cancers.

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Demographics

Triple negative breast cancer is most frequent in African American women. Roughly 40% of breast cancers in African American women are triple negative compared to roughly 15% in Caucasian women. Another difference in African-American women who get triple negative breast cancer is that most of them are pre-menopausal.  One other demographic group that is prone to have triple negative breast cancer are women who have BRCA1 mutations.

Triple negative breast cancer is most frequent in African American women. Roughly 40% of breast cancers in African American women are triple negative compared to roughly 15% in Caucasian women. Another difference in African-American women who get triple negative breast cancer is that most of them are pre-menopausal.  One other demographic group that is prone to have triple negative breast cancer are women who have BRCA1 mutations.

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Genetics

The association between BRCA1 mutations and triple negative breast cancers has led to research looking for a genetic predisposition to develop these types of cancers. Studies have identified specific locations within genes that appear to be abnormal in a higher proportion of cases than in other types of breast cancer. However, other than the BRCA1 gene, a specific gene causing this type of cancer has not been identified. It is likely that a combination of genetic factors located in specific locations within the genome interactively play a role in the development of TNBC. Genetics is an active field of investigation in TNBC.

The association between BRCA1 mutations and triple negative breast cancers has led to research looking for a genetic predisposition to develop these types of cancers. Studies have identified specific locations within genes that appear to be abnormal in a higher proportion of cases than in other types of breast cancer. However, other than the BRCA1 gene, a specific gene causing this type of cancer has not been identified. It is likely that a combination of genetic factors located in specific locations within the genome interactively play a role in the development of TNBC. Genetics is an active field of investigation in TNBC.

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Biology

Although much is written about the inferior prognosis of triple negative breast cancers compared to other types of cancer, it's important to keep in mind that stage for stage, their prognosis is still fairly similar to the other sub-types. Part of the reason has to do with the fact that hormone blocking agents are not effective due to the lack of estrogen and progesterone receptors.

Historically, these tumors exhibit an aggressive biologic behavior and are associated with a lower survival, more rapid relapse rate and aggressive behavior. Part of the reason has to do with the fact that hormone blocking agents are not effective due to the lack of estrogen and progesterone receptors.

Although slightly more aggessive in their behavior, these tumors are very receptive to the effects of chemotherapy and patients will visibly noticed how their tumor disappears even after one or two cycles of treatment. Biologically, we also know that those patients that exhibit a pathologic complete response (PCR) have a better prognosis than those who don’t. A pathologic complete response is considered to be present when chemotherapy is administered prior to surgery and at the time the surgery no residual cancer is identified. The responsiveness to chemotherapy is why almost all patients with TNBC are treated with chemotherapy.

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Prognosis

It is true that Triple Negative Breast Cancer (TNBC) affects young patients, may have a slightly more aggressive behavior than other types of breast cancer and has no option for hormonal manipulation. You may read many gloom and doom posts and publications about the disease.

However, there are many positive aspects of having a Triple Negative Breast Cancer. For instance, about 30 to 40% of patients will achieve a complete pathologic response with neo-adjuvant chemotherapy and this selects them as patients with a favorable outcome. Recently, immunotherapy has become an option for patients with Triple Negative metastatic breast cancer and based on results from other cancers such as melanoma and lung cancer, there's reason to be optimistic about the effects of immunotherapy. Ultimately, the prognosis of your Triple Negative Breast Cancer (TNBC) will be determined by the stage of the disease and the response to therapy. As with all other breast cancers, the earlier the stage, the better the prognosis. Do not be discouraged by the negative assessment you will read about on-line and discuss with your doctor the positive aspects of your disease and your stage of disease.

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