Science Series #13: Incidence and mortality rates of breast cancer

What is breast cancer?

Cancer is caused by mutations that are either inherited or acquired in genes. Breast cancer, like all other cancers, is an uncontrolled growth of abnormal breast cells that are either malignant or benign. Benign tumors are not cancerous and therefore not life-threatening. However, some of these can become malignant, hence increasing a women’s chance of getting breast cancer. Breast cancer cells form in either the lobules which function to produce milk, or the ducts that carry milk from the lobules to the nipple. They can also form in the stomach tissue, however it is less common as opposed to the lobules and ducts.

(Source: American Cancer Society)

Risk factors

Breast cancer is usually caused by errors that happen in the genes of an individual. An estimate of 85% of breast cancers occur in women that possess genetic mutations that occur as a result of the aging process and lifestyle choices, such as obesity, consuming alcohol, poor dietary habits, exposure to carcinogenic chemicals, and smoking. As women grow older, their chances of breast cancer increase, especially women over the age of 40 years.

All women are at risk, yet those with a family history of breast cancer are at a higher risk. Approximately 5-10% of breast cancers are linked to gene mutations that are inherited from one´s parents. The most common mutations occur in the BRCA1 and BRCA2 genes whereby on average, women that possess the BRCA1 gene have an estimated 72% lifetime risk of developing breast cancer, and women that possess the BRCA2 gene mutation have risk of approximately 69%.

(Source: Breastcancer.org and World Health Organization)

Estimated global incidence rates

Breast cancer has been increasing globally and as of 2020, it has surpassed lung cancer, becoming the most commonly diagnosed cancer amongst women. According to the World Health Organization (WHO), more than 2.3 million women were diagnosed in 2020 with breast cancer. Furthermore, it now represents 12.5% of all new cancer cases that were diagnosed in that year, where there were approximately 2.26 million new cases worldwide among men and women. It is the most common cancer in women worldwide contributing to 25.8% of all new cases diagnosed in 2020. In comparison to the global contributions of breast cancer, in the United States (U.S.), breast cancer represents 15% of all new cancers.

(Source: World Health Organization and World Cancer Research Fund)

Estimated incidence rates in the U.S.

Approximately 281,550 new cases of invasive and 49,290 new cases of non-invasive breast cancers were diagnosed in women in the U.S. in 2021. In this country a woman’s lifetime risk of developing breast cancer is about 1 in 8 (13%) and a man’s lifetime risk is about 1 in 833. Recent data suggest an estimated 287,850 women, and 2,710 men will be diagnosed with breast cancer in 2022.

Incidence rates for invasive breast cancer have been increasing by 0.5% per year since the mid-2000s. The highest number of estimated new cases was found in California to be 31,720 and the lowest number of cases was found in Wyoming to be 460. 

(Source: Cancer.org and Breastcancer.org)

Estimated global mortality rates

As opposed to incidence rates, breast cancer mortality rates show that it is the second leading cause of cancer death in women. The probability of a woman dying from breast cancer is about 1 in 39. In 2020, there were approximately 685,000 deaths globally. During the years 2015- 2019, the death rate was 19.9 per 100,000 per year for all races.

(Source: Seer.cancer.gov)

Estimated mortality rates in the U.S.

In 2021, an estimate of about 43,600 women in the U.S. died from breast cancer. In 2022, the death rate is predicted to be approximately 43,780 breast cancer deaths, 43,250 of which will be women and 530 men. California has the highest number of estimated deaths for breast cancer in 2022, 4,690, whereas the state with the least estimated number of deaths in Alaska, North Dakota, and Wyoming with 70 deaths. It is important to highlight, since the death rate peak in 1989, the rate has declined by 42% as of 2019.

The trends in the death rate show a steady rate in women under the age of 50 since 2007, however as the age of women increases, the mortality rate decreases. Between 2013- 2018, the death rate decreased by 1% per year.

(Source: Cancer.org and Breastcancer.org)

Comparison between incidence rates of developed and developing countries

Based on 2020 statistics, Australia and New Zealand had the highest incidence rate of 95.5 per 100,000 population whilst South-Central Asia had the lowest rate of 26.2 per 100,000 population. The rate of incidence varies between high-income and low-income countries such that high-income countries display an incidence rate of 81.0 per 100,000 population whilst low-income countries display a rate of 33.8 per 100,000 population. In high income countries, one prominent and proven successful method to reduce mortality rates is early detection of breast cancer. For instance, statistics show that the survival rate for 5 years after diagnosis is 90% in high-income countries, and countries such as India and South Africa have 66% and 40% respectively. Low-income countries have a higher mortality rate of 18.3 per 100,000 population whilst high-income countries have a rate of 12.9 per 100,000 population. Treatment options are also linked to higher mortality rates in low-income countries. These countries have limited resources to perform standardized treatments. The triple-negative breast cancer subtype also contributes to the variations in mortality rates; triple-negative breast cancer does not express any hormone receptors positives, nor does it express the human epidermal growth factor receptor 2 (HER2) gene, rather it possesses a mutation on the BRCA1 gene which makes it much more difficult to treat thereby often leading to death.

(Source: World Health Organization)

Treatments

Treatment options vary based on the location of the cancer cells as well as their subtypes. The location of the cells determines the behaviour and development of cancer. Ductal carcinoma and lobular carcinoma can be invasive and non-invasive hence both types should be treated. Once diagnosed with breast cancer, a patient would undergo a breast tissue biopsy to determine which type of breast cancer they possess.

There are two types of treatments, i.e., local treatments, which treat the tumor without affecting any other part of the body, and systemic treatments, which are drugs that are administered orally or intravenously to target the cancer cells. The local treatments are surgery and radiation. Surgery is a standardized treatment option for most breast cancers. Either one of the two types, mastectomy or breast-conserving surgery, is conducted first in most cases, followed by radiation given externally to a portion of the breast using external beam radiation therapy or internally by inserting radioactive seeds for a short time using brachytherapy.

(Source: Cancer.org and Breastcancer.org)

Systemic treatments follow shortly after local treatments or sometimes before surgery. These treatments are chemotherapy, hormone therapy, targeted drug therapy, and immunotherapy. Chemotherapy is the main systemic treatment option, and it is done using anti-cancer drugs that are administered intravenously into the bloodstream to reach and kill cancer cells. Hormone therapy targets estrogen and progesterone which are used by cancer cells to grow. Hormone receptor-positive cells are treated by either blocking the hormone receptors or lowering their levels to inhibit the growth of the cancer cells. Targeted drug therapy is another option that directly targets the proteins which aids in the growth of cancer cells, such as the HER2 protein. Three types of drugs are used to treat patients presented with HER2-positive breast cancer. One drug that is administered acts by injecting monoclonal antibodies, which attach to the HER2 proteins and prevent them from growing. The second type is antibody-drug conjugates which are monoclonal antibodies that are linked to chemotherapy drugs, and they act as signals to draw the chemotherapy drug to the HER2 protein. The third type is kinase inhibitors which are used to block the kinases on the cancer cells to prevent growth signals from reaching the cells.  

(Source: Cancer.org and cancerresearch.org and clevelandclinic.org and cancer.net)

Immunotherapy is an emerging hallmark of breast cancer. It plays a vital role in the treatment and prevention of breast cancer. This type of treatment works by stimulating the immune system to provide an immune response against cancer cells. Tumor microenvironments are largely orchestrated by inflammatory immune cells. Long-lasting chronic inflammation provides conditions that increase the risk of cancer by causing sustained cell proliferation, increasing the presence of growth factors, causing changes in surrounding tissue and proteins, creating activated stroma, and leading to the invasion and activation of inflammatory immune cells. Cancer cells can evade the immune system by appearing as normal cells and therefore immunotherapy is used to initiate an immune response at the site where cancer cells are.

(Source: Cancer.org and cancerresearch.org and clevelandclinic.org)

Immunotherapy is divided into cellular, molecular, and vaccination therapies. Cellular therapies are most beneficial to patients presenting with metastatic melanoma. It involves adoptive T cell therapy and the blocking or deletion of regulatory T cells. Molecular therapies make use of the cytokine IL-2 molecule, agonists of co-stimulatory receptors, and checkpoint inhibitors. Checkpoint inhibitor drugs stop the binding of checkpoint proteins such as PD-1 and CTLA-4 from binding to their respective proteins on cancer cells so that T cells can initiate an immune response against the cancer cells. Vaccination therapy is mostly used as a preventative measure, and as a treatment for pre-existing cancers. This therapy aims to boost one’s own immune system to fight off the disease. ConvitVax is an example of a vaccine that is being developed to treat breast cancer.

(Source: Cancer.org and cancerresearch.org and clevelandclinic.org)

JCWO’s response to breast cancer

Since its inception in 2014, JCWO is contributing to the fight against breast cancer, targeting especially underprivileged female patients in poor developing countries, where mortality rates are higher for this disease due to poor diagnostics and/or inaccessible treatments.

Through its Cancer Immunotherapy program, the organization is currently developing a simple and low cost personalized breast cancer therapeutic vaccine, named ConvitVax, that combines the patient’s whole tumor cells, bacillus Calmette Guérin (BCG) and low concentrations of formalin; to stimulate the immune system and potentially achieve an effective and specific response against tumor cells, with minimal to no side-effects, and a possible establishment of immune memory.

According to its philosophy, based on a humanistic approach to science and the desire to build a stronger society with equal access to healthcare,  JCWO´s core work is focused on potentially providing a free modern treatment to women with the disease.

Studies conducted on ConvitVax have shown promising results, both in animal models and a small patient pilot study. This immunotherapy is approved by the U.S. Food and Drug Administration to begin a phase 1 clinical trial on 40 women with stage IV breast cancer. A new submission for approval of a phase 1b/2 clinical study in females with metastatic breast cancer is currently in progress.

The first clinical trial is expected to be carried out in Venezuela, where  according to the latest Global Cancer Statistics in 2020, breast cancer represented 28.3% of all cancers in females, making this disease the first most diagnosed cancer in this country. In 2021 the Sociedad Anticancerosa de Venezuela published a report showing that the mortality rate for this disease was 19.01 compared to 12.9 in high-income countries. Furthermore, in the same year, an increase in both mortality (18%) and incidence (0.3%) were reported for cancer rates in women compared to the baseline values of 2014.

For more information on JCWO´s contributions to the fight against breast cancer, visit our website.

(Source: World Health Organization; jacintoconvit.org and cancervenezuela.org)

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