Triple Negative Breast Cancer Types detection and diagnosis
Posted By HealthcareOnTime Team
Posted on 2021-09-16
What is Triple Negative Breast Cancer?
In our body, cell division is kept under very strict vigilance, both by the same
cell, as well as by those of the Immunity
system. Since the signal for a cell to
divide (or stop dividing) begins from the DNA level, it is of no surprise that
gene mutations play a large role in the development of cancer
. In some cancers,
the cells exhibit receptors on their surface which bind to external signals
and turn on cell proliferation. If the receptors for these growth promoting
signals are over-expressed due to genetic mutations, cells proliferate more.
An advantage of such types of cancer is, one can target these overexpressed
receptors and block them to prevent the increased signal from causing
uncontrolled cell growth. This is the basis of several protocols that are
used for treatment of cancer. However, some cancers may also develop
without expressing such receptors. Needless to say, the treatment of
such cancers is more challenging. One example of this type of cancers
is triple negative breast cancer
What does it mean when breast cancer is triple-negative?
Book CA 15.3 Breast Cancer marker test
The classification of cancer types is done by techniques such as microarray
analysis and next genome sequencing. These techniques allow cancers to
be distinguished based on the molecular markers (molecules present in/on
surface of these cells that distinguish them from other cells) they carry.
In this way, breast cancers can be either estrogen (ER) positive or estrogen
negative, based on whether they have estrogen receptor, or not. Molecular
markers also dictate the treatments that can be used for that particular
type of cancer. Thus, Tamoxifen is a drug that is used as a part of hormone
therapy for those cancers that exhibit hormone receptors. Another
example is Herceptin for cancer cells that overexpress HER2. A similar
type of breast cancer is Triple Negative Breast Cancer. It is one of the most aggressive types of
breast cancer. Widely considered as an orphan disease, Triple Negative Breast Cancer is
characterized by the absence of three receptors on the surface of
the cancer cells. These receptors are estrogen receptors, progesterone
receptors, and epidermal growth factor receptor 2 (HER-2/neu).
Triple Negative Breast Cancer is a major cause for concern in India, as it has a prevalence
of 43.5%. Since these cancers do not respond to hormones
development of long-term therapeutic strategies is the need of the hour.
Who is most at risk for triple-negative breast cancer?
- Triple Negative Breast Cancer usually presents at a younger age (premenopausal women, lower than 50 years)
as compared to non-Triple Negative Breast Cancers.
- These tumors are larger in size as compared to other tumors at the time of
presentation and are also diagnosed at later stages (stage III). Triple Negative Breast Cancers are
therefore more rapid growing and aggressive.
- Triple Negative Breast Cancers are associated with BRCA1 mutations, and are more common in some ethnicities
than others. The highest percentage of Triple Negative Breast Cancer cases is reported to be in India.
- Many casesof Triple Negative Breast Cancer are also reported to show node involvement
(spread of the cancer to lymph nodes).
- The recurrence of cancer after treatment of Triple Negative Breast Cancer is reported to occur earlier
than recurrences of other cancers. However, the higher risk is present only
for 2 to 3 years after treatment and starts to decline after 5 years'. Triple Negative Breast Cancers
generally have poorer prognosis, and metastasis also occur earlier in
Triple Negative Breast Cancers as compared to other cancers.
- Triple Negative Breast Cancers are reported to respond better to chemotherapeutic drugs, which is
the main mode of treatment of Triple Negative Breast Cancer. Those most at risk of Triple Negative Breast Cancer are...
- People who have BRCA1 and BRCA2 mutations
- Younger women (under 50 years of age)
- Asians (including Indians), Hispanics and African Americans
- Those with previous history of breast cancer
- As per some studies, reproductive factors like higher number of children, reduced
breast feeding, greater use of oral contraception, being premenopausal are also linked with Triple Negative Breast Cancer
What are the different types of triple negative breast cancer?
Gene expression studies have been carried out to understand the extent of
heterogeneity of Triple Negative Breast Cancer. While most of cells found in Triple Negative Breast Cancer tumor (70%) are
basal like cells, other subtypes of cells are also found in Triple Negative Breast Cancer. Classification
by Lehman and colleagues has divided Triple Negative Breast Cancer into 7 different subtypes.
These subtypes are:
- Basal-like 2 (B12)
- Immunomodulatory (IM)
- Mesenchymal (M)
- Mesenchymal Stem-Like (MSL)
- Luminal Androgen Receptor (LAR)
- Unstable Subtype (UNS)
The division of Triple Negative Breast Cancer into these subtypes can also assist in therapy selection
as they are based on gene expression profile. For instance, basal-like tumors
are characterized by the increased activation of pathways of cell cycle and DNA
damage response (ATR and BRCA). In these subtypes, targeting DNA damage
pathways, therefore, is an effective therapeutic approach. Two agents that are
used for this treatment protocol are platinum salt and PARP inhibitors. Platinum
based therapeutic agents are also being tested for treatment of metastatic Triple Negative Breast Cancer.
How is triple negative breast cancer detected and diagnosed?
Is there treatment for triple-negative breast cancer?
Currently no screening techniques are used specifically for Triple Negative Breast Cancer, routine
self-examination of breast is ideally recommended to look out for suspicious
masses for breast cancer in general. Genetic testing may sometimes be done
but is not recommended for routine screening. Imaging techniques used for
identifying Triple Negative Breast Cancer are the same as other types of breast cancers, but Triple Negative Breast Cancer
present with different imaging features.
Triple Negative Breast Cancer infrequently or rarely show the spiculated margins, irregular shape
and calcifications that are exhibited by other breast cancers. Despite being
larger in size, Triple Negative Breast Cancer tumors may remain hidden in the mammogram in some
cases. Some Triple Negative Breast Cancer tumors may show circumscribed and microlobulated
margins, focal asymmetry and a mass associated with calcifications (isolated calcifications are rare).
highly sensitive for detection of Triple Negative Breast Cancer, the tumor presents as a discrete
mass lacking suspicious sonographic features
also extremely sensitive for Triple Negative Breast Cancer, MRI scans show the morphological features
of Triple Negative Breast Cancer more clearly. Triple Negative Breast Cancer mass is most commonly reported to be oval or
round shaped with dominant margins. In addition, biopsy can be done for
confirmation of Triple Negative Breast Cancer diagnosis.
The absence of cell surface receptors in Triple Negative Breast Cancer means that this type
of cancer does not respond to hormone therapy which are commonly
used for treatment of breast cancer. These treatments target hormone
and growth factor receptors which are overexpressed in most cancer cells.
Hormonal therapies and HER2-targeted therapies inhibit the proliferative
effect that estrogen, progesterone
and HER2 have on breast cells. Inhibiting
the proliferation of cancer cells helps to reduce the spreading of tumor.
- Current treatment for triple-negative breast cancer
Treatment for Triple Negative Breast Cancers usually requires combination therapies and involves
radiotherapy, chemotherapy, and surgery. Triple Negative Breast Cancers respond better to neoadjuvant
therapy, in which chemotherapy drugs are administered before surgery to
reduce tumor size. Surgery is done to remove the tumor, either by removing
the whole breast (mastectomy) or removing the lump (lumpectomy). The
surgery may be followed further by chemotherapy to eradicate any cancer
cells that may have spread into other parts of the body. Radiation treatment
can be done following lumpectomy. Immune therapy is also practisedfor
treatment of some subtypes of Triple Negative Breast Cancer.
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Future Aspects treatment for Triple Negative Breast Cancer
Some of the treatment strategies that are currently being investigated for Triple Negative Breast Cancer involve:
- Targeting the BRCAness of Triple Negative Breast Cancer-
since Triple Negative Breast Cancers are associated with BRCA mutation, treatment with
agents such as PARP inhibitor has shown promising results. BRCA
is a gene involved in DNA damage repair. In the absence of BRCA,
the cancer cell has to turn to PARP based pathway to repair its
damaged DNA. This process can be inhibited by using PARP
inhibitors, which prevents cancer cells from repairing damage
to their DNA and succumbing to that damage.
- Inhibitors of PAM pathway-
the PAM pathway controls the cell cycle from survival to cell death
and is therefore important in the formation of tumor and its progression.
Activation of the PAM pathway often results in development of chemoresistance in breast cancer.
- EGFR inhibitors.
Epidermal Growth Factor Receptor 1 (HER1) is markedly overexpressed in
Triple Negative Breast Cancer, which contributes to its poor prognosis. HER1 proteins
could be targeted
by monoclonal antibodies
and/or tyrosine kinase