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Introduction To Chemotherapy

Chemotherapy is one of the many options available to treat cancer. Chemotherapy involves using drugs to stop cancer cells in the body from growing, multiplying, dividing, and spreading. Chemotherapeutic drugs are of different types, and not all of them work in the same way. 

While chemotherapy affects the cancer cells, the drugs used in the treatment cannot differentiate between normal and cancerous cells, which results in some damage to healthy cells and tissues. 

The most common example of this is the loss of hair in people undergoing chemotherapy treatment. 

Around 10% of patients undergoing chemotherapy for breast cancer experience severe chemotherapy-induced alopecia.  

Though chemotherapy is one of the primary treatment options for cancer, other newer treatments may be preferred for certain types of cancer.

Breast Cancer Chemotherapy

Chemotherapy is used as one of the main treatments for breast cancer cases, during which drugs are used to target and destroy breast cancer cells. 

The drugs may be administered orally (by mouth) or intravenously (injected directly into the veins). 

In most breast cancer cases, chemotherapy is used alongside surgery, radiation, and hormone therapy. 

Chemotherapy improves breast cancer treatment outcomes and allows the individual to live longer and enjoy a better quality of life. 

However, chemotherapy administered for breast cancer can have side effects, which may be mild and temporary. 

In breast cancer cases, chemotherapy may be given in the following scenarios:

  1. Before surgery

Chemotherapy may be given before breast cancer surgery to reduce the tumor’s size and make it easy to remove with a less extensive surgical procedure. This procedure is called neoadjuvant therapy and is used to remove large breast tumors.

  1. After surgery

In some cases, chemotherapy is given after a surgical procedure has been done to remove the tumor. This is called adjuvant chemotherapy, and it is shown to reduce any remaining cancer cells that may have been left behind after the surgery. Chemotherapy given after a breast cancer removal surgery reduces the chances of recurrence.

  1. In advanced breast cancer cases

Chemotherapy is the primary treatment of choice in advanced breast cancer cases where cancer has spread outside the breast to the underarm area.

Common Drugs Used in Adjuvant and Neoadjuvant Therapies include:

Chemotherapy drugs used in the treatment of advanced breast cancer include:

Early breast cancer cases are usually treated with a combination of chemotherapeutic drugs, but advanced cases of the disease are mostly treated with single drugs. 

If breast cancer has been diagnosed as HER-positive (Hormone Receptor-Positive), chemotherapy drugs may be supplemented with one or more drugs targeting the HER-2 receptors.

Why Does Hair Loss Occur In Chemotherapy?

Chemotherapy for any type of cancer, including breast cancer, can have side effects. Some common side-effects of chemotherapy include:

Hair loss, also called alopecia, is very common during breast cancer chemotherapy. This happens because the chemotherapy drugs target rapidly dividing cells– both healthy and cancerous cells. 

Hair follicles are one of the many rapidly dividing cells in the body found in the skin. When chemotherapy drugs are looking to destroy any rapidly dividing cells, they also destroy hair follicles. This results in hair thinning and loss after a few days of chemotherapy. Hair loss usually happens very quickly following just a few chemotherapy sessions.

How Does Genetics Influence Hair Loss Due To Breast Cancer Chemotherapy?

Analyzing genetic risk factors can help develop an effective way to reduce chemotherapy-induced alopecia in breast cancer patients. 

The ABCB1 Gene

ATP-binding Cassette Subfamily B Member 1 is a part of the ATP-Binding Cassette family of genes. These genes make proteins (called ABC proteins) that help transport various molecules across cell membranes in multiple tissues

These ABC proteins also help decrease the accumulation of xenobiotic compounds (compounds not produced by the body and are found in the body) like drugs in the case of multidrug-resistant.

rs1202179 is a Single Nucleotide Polymorphism, or SNP found in the ABCB1 gene located on chromosome 7. 

The C allele of this SNP has been linked to a decrease in the expression of the ABCB1 and subsequent increased risk of chemotherapy-induced alopecia (pCIA) in women being treated for breast cancer.  

This effect is due to the accumulation of transporting drugs like docetaxel, resulting from P-glycoprotein deficiency. P-glycoprotein is a protein produced by the ABCB1 gene to eliminate the drug. 

Deficient P-glycoprotein causes an increased exposure of hair follicles to docetaxel damage, resulting in hair fall.

The PCDH15 Gene

Protocadherin-related 15 or PCDH15 is a gene that gives instructions for the production of membrane proteins.

These membrane proteins are responsible for retinal and cochlear functions and maintaining calcium-dependent adhesion between cells in the body.

The presence of the G allele in SNP rs7919725 in the PCDH15 gene increases the risk for drug-induced grade 2 alopecia.

The TMEM132C Gene

Transmembrane Protein 132C or TMEM132 C is located on chromosome 12. It plays a role in cell adhesion, i.e., how cells attach to their neighboring cells.

rs11059635 is an SNP in the TMEM132C gene. The G allele of this SNP plays a role in chemotherapy-induced alopecia due to its response to Paclitaxel.

The CACNB4 Gene

Calcium voltage-gated channel auxiliary subunit beta 4 or CACNB4 is a gene that provides instructions for making calcium channels

Calcium channels are essential for transporting calcium ions inside the cells. They enable cells to generate and transmit electrical impulses for muscle contractions, cell-to-cell communication, and regulate genes. 

Therefore, any abnormal changes in the CACNB4 gene can cause neurological and muscular conditions.

rs3820706 is an SNP in the CACNB4 gene and is located on chromosome 2.

The G allele of SNP rs3820706 plays a role in chemotherapy-induced alopecia.

Non-Genetic Factors Influencing Hair Loss Due To Breast Cancer Chemotherapy 

Non-genetic factors that influence hair loss during breast cancer chemotherapy include:

Preventing Hair Loss Due To Breast Cancer Chemotherapy

Hair loss during chemotherapy is dreaded by many women undergoing treatment for breast cancer. Many methods have been studied that can prevent hair loss due to breast cancer chemotherapy. These include:

In this method, ice packs or an ice cap are placed on the scalp during a chemotherapy session. These help contract the blood vessels in your scalp to prevent the chemotherapy drugs from reaching your hair follicles.

Some studies have shown that this prevention method is applicable only with certain chemotherapeutic drugs like taxanes. A study published in 2017 in the Journal of the American Medical Association stated that using scalp cooling in women with stage I and II breast cancer resulted in less than 50% hair loss after the fourth chemotherapy session.

Scalp cooling or using ice caps has its side effects, such as discomfort or headaches due to the cold.

Another method to prevent hair loss during breast cancer chemotherapy is scalp compression. This method may be used with or without scalp cooling. Clinical trials are still underway to determine the effectiveness of scalp compression on hair loss prevention but what is known so far is that this method is less effective than scalp cooling.

Medications are often recommended to manage hair loss caused due to breast cancer chemotherapy. These medications do not prevent hair loss but help in faster regrowth. Common medications that help hair regrowth include topical application of 2% Rogaine (minoxidil) and Panicum miliaceum.

Summary

  1. Chemotherapy is one of the primary treatment modalities for breast cancer.
  2. In chemotherapy, certain medications are used either before or after breast cancer surgery to increase the longevity of the individual and decrease the chances of breast cancer recurrence.
  3. Chemotherapy is also used in advanced breast cancer cases.
  4. One of the significant side effects that most women undergoing chemotherapy for breast cancer are worried about is hair loss (also called chemotherapy-induced alopecia).
  5. Chemotherapy-induced alopecia occurs because the drugs used during treatment target rapidly dividing cancer cells but cannot differentiate between rapidly dividing healthy cells like hair follicles. This results in hair thinning and loss.
  6. Some genes that influence chemotherapy-induced hair loss are ABCB1, PCDH15, TMEM132C, and CACNB4.
  7. Non-genetic factors that influence hair loss during chemotherapy include the drugs used during chemotherapy, the combination of medications used, pre-existing medical conditions that you may have, your lifestyle factors, and frequency of chemotherapy.

References

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