Breast cancer chemoprevention
The World Health Organisation (WHO)’s three pillars on breast cancer awareness are early detection, early diagnosis, and comprehensive treatment. I will be using materials from a paper by Dana et al for this piece. The role of polyphenols in overcoming cancer drug resistance: a comprehensive review. Cellular & Molecular Biology Letters (2022) 27:1
Management of breast cancer
Localised solid tumors are often treated with surgery in their early stages. However, other treatment modalities are applied at advanced stages and/or following the surgery, such as targeted therapies, radiotherapy, immunotherapy, and chemotherapy. Advances made in the field of antitumor agents have led to a significant increase in patients’ life quality and disease-free survival.
Challenges
Despite the importance of chemotherapeutic drugs, there are significant drawbacks in using them to treat cancer, such as solubility and instability of drugs, nonspecific drug delivery, and adverse effects due to systemic toxicity. [Furthermore, recurrence and relapse of cancer occur in some patients even after a favourable response at the beginning of the treatment. Acquired drug resistance has become an important challenge that results in the failure of cancer treatment. Both acquired and intrinsic processes can lead to chemoresistance in cancer cells.
Acquired drug resistance indicates a newly developed resistance against a therapeutic approach that was effective at the beginning. Intrinsic chemoresistance involves a pre-existing factor that causes a drug to be inefficient. Tumor cells’ heterogeneity is one of the factors leading to chemoresistance.
Stem-like cancer cells are renewable subpopulations of tumour cells that are responsible for heterogeneity. There are various cell generations within one tumor, and each clone is sensitive to chemotherapeutic agents to some degree. Therefore, targeting tumor cells with a single agent may not lead to a favourable response. Increased drug efflux, changes in the target of drugs, apoptosis, and repair signaling pathways are other mechanisms involved in the resistance of cancer cells to chemotherapeutic drugs. This explains the use of combination therapy in the management of cancer. Cancer cells use several mechanisms to evade chemotherapeutic agents. This explains the increased interest in the use of chemopreventive agents. A notable example is a polyphenol-rich food.
Polyphenols
Polyphenols attack cancer cells in a variety of ways and confront many cancer hallmarks. The antioxidant impacts of polyphenols are through either scavenging free radicals or building a barrier against their generation. The main free radicals that exist in our cells and cause oxidative stress are reactive oxygen species (ROS) and reactive nitrogen species (RNS).
Polyphenols also have the capacity to inhibit the generation of ROS and RNS by interfering with the enzymes involved in their production. As regards apoptosis (programmed cell death), a great number of polyphenols are able to induce cell death by altering the expression of apoptosis-related genes.
Cell cycle arrest is another anti-cancer effect of these polyphenol-rich foods. Metastasis is a series of concurrent mechanisms which help the tumour cells gain the ability to migrate from their primary site to other sites of the body and increase the cancer lethality. Cellular motility, hypoxia, and angiogenesis are the primary mechanisms that prepare tumoral cells for infiltration. Polyphenols have shown their capabilities in influencing several steps of this process.
Epigenetic dysregulations and abnormalities are the basis of tumor initiation, progression, and resistance to therapy. Epigenetics refers to changes in gene expression that do not involve alterations to the underlying DNA sequence. These changes can be influenced by various factors, including environmental exposures, lifestyle, and aging.
Polyphenols can affect different aspects of cancer drug resistance. Facilitation of diffusion, passive transfer, and active transport are different types of drug absorption to the tumor cells. Decreased drug uptake is a mechanism by which tumoUr cells develop chemoresistance against therapeutic agents. The reduced tendency for binding to drugs is a common process that leads to decreased drug absorption.
Another mechanism is decreased number of transporters. Drug formulations based on nanotechnology have attracted a lot of attention in recent years due to various reasons, such as targeted drug delivery, ability to encapsulate multiple agents, higher biocompatibility, decreased side effects, and slow-release rate. Another important advantage of nano-formulations is the ability to enhance bioavailability of drugs and overcome chemoresistance. Among other beneficial effects, nano-formulations lead to an increase in cellular drug uptake. Several studies have been conducted on the role of polyphenols in designing nanomaterials for drug delivery.
Risk factors for breast cancer
Risk factors you cannot change
These are- Getting older. The risk for breast cancer increases with age. Most breast cancers are diagnosed after age 50, Genetic mutations. Inherited changes (mutations) to certain genes, such as BRCA1 and BRCA2 increased risk of breast and ovarian cancer; Reproductive history. Starting menstrual periods before age 12 and starting menopause after age 55 expose women to hormones longer, raising their risk of getting breast cancer; Having dense breasts. Dense breasts can sometimes make it hard to see tumours on a mammogram. Women with dense breasts are also more likely to get breast cancer, Personal history of breast cancer or certain noncancerous breast diseases. Women who have had breast cancer are more likely to get breast cancer a second time. Some noncancerous breast diseases such as atypical ductal hyperplasia or lobular carcinoma in situ are associated with a higher risk of getting breast cancer; Family history of breast or ovarian cancer. Having a family history of breast cancer may increase risk for breast cancer; Previous treatment using radiation therapy. Women who had radiation therapy to the chest or breasts (for instance, treatment of Hodgkin’s lymphoma) before age 30 have a higher risk of getting breast cancer later in life; Exposure to the drug diethyistilboestriol (DES). DES was given to some pregnant women in the United States between 1940 and 1971 to prevent miscarriage. Women who took DES have a higher risk of getting breast cancer. Women whose mothers took DES while pregnant with them also may have a higher risk of getting breast cancer.
Risk factors you can change
These are- Not being physically active. Women who are not physically active have a higher risk of getting breast cancer; Being overweight or having obesity after menopause. Older women who are overweight or have obesity have a higher risk of getting breast cancer than those at a healthy weight; Taking hormones. Some forms of hormone replacement therapy (those that include both estrogen and progesterone) taken during menopause can raise risk for breast cancer when taken for more than 5 years. Certain oral contraceptives (birth control pills) also have been found to raise breast cancer risk; Reproductive history. Having the first pregnancy after age 30, not breastfeeding, and never having a full-term pregnancy can raise breast cancer risk; .Drinking alcohol. Studies show that a woman’s risk for breast cancer increases with the more alcohlo she drinks.
Research suggests that other factors such as smoking, being exposed to chemicals that can cause cancer,
Consume more polyphenol-rich foods
With all these risk factors and complexities in the management of cancers (breast), it is important to consume polyphenol-rich foods to boost one’s body against cancer and to enhance the capacity to cope with issues associated with its management. Cocoa is an excellent source of polyphenols.
DR. EDWARD O. AMPORFUL
CHIEF PHARMACIST
COCOA CLINIC
BY DR. EDWARD O. AMPORFUL