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Improving screening, survival in BCa patients in South Africa

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Women in Africa present with BCa at a mean age of around 35- to 45 years, compared to their counterparts living in high-income countries (mean of 45- to 60-years) and present with more advanced disease (in South Africa, 50%-55% of women present with advanced BCa).3

Although mammogram screening from the age of 40 has been shown to save countless lives by reducing the incidence of advanced and inoperable disease with metastases, the uptake in LMICs is low with less than 2.2% of women between the ages of 40- to 69-years having undergone screening.2,3

According to Prof Jennifer Moodley, Director Cancer Research Initiative at the Faculty of Health Sciences at the University of Cape Town, studies have shown that time to a cancer diagnosis may be influenced by several factors including women’s knowledge and awareness of cancer symptoms, whether women see themselves as being at risk for BCa, barriers in the health system, knowledge and attitude of health providers, and psychological, and socio-cultural barriers to healthcare.2

The downside of screening, writes Dr Shirley Lipschitz, considered one of South Africa's most well- regarded and experienced breast-imaging specialists, is that it can result in overdiagnosis and overtreatment. The American Cancer Society (ACS) and the United States Preventive Services Task Force (USPSTF) consider mortality reduction as the only benefit of screening.4

Some studies show that BCa mortality can be reduced by between 30%–40%, while others show a reduction of 25% decrease in those invited to screening and a 38% reduction in those actually exposed to screening.4

Yet another study showed that mortality decreased by 44% in women aged between 40- to 49-years, 40% in those in the 50–to 59-year age group, 42% in women between 60– to 69-years and 35% in those in the 70–79 age group.4

According to Dr Lipschitz, overdiagnosis and overtreatment of a cancer are perceived as harms of screening.4

The American College of Obstetricians and Gynecologists (ACOG) states that reported rates of overdiagnosis range from 1% to 10% and expose women to unnecessary call backs and biopsies, which incurs great costs, and stress. The USPSTF found that one in eight women diagnosed with BCa with biennial screening from ages 50- to 75-years will be overdiagnosed.5

Furthermore, state the body, for every woman who avoids a death from BCa through screening, two to three women will be treated unnecessarily. Overtreatment, are in part, related to the management of ductal carcinoma in situ.5

According to Dr Lipschitz, improved technology, especially with digital breast tomosynthesis, will enable more screening detected cancers with less call backs and biopsies.3

Guideline screening recommendations

The goal of screening is to detect preclinical disease in healthy, asymptomatic patients to prevent adverse outcomes, improve survival, and avoid the need for more intensive treatments.5

Breast self-examination, breast self-awareness, clinical breast examination, and mammography all have been used alone or in combination to screen for BCa.5

The ACOG recommends regular screening mammography annually or biennially, starting at age 40 years in women at ‘average’ (see box 1) risk of BCa. The USPSTF recommends biennial screening from the age of 50.5

The ACS recommends screening from the age of 40- to 45-years and stopping if life expectancy is >10-years. The ACS recommends yearly screening for women between the ages of 40- and 54-years, and as an ‘option’ for women >55-years.5

The European Commission Initiative on Breast Cancer recommends mammography for women aged 50- to 69-years and with conditional recommendations for women in younger and older age groups.6

The European Society of Medical Oncology (ESMO) recommends regular (annual or biennial) mammography in women aged 50- to 69-years. Regular mammography may also be done for women aged 40- to 49-years and 70- to 74-years, although the evidence for benefit is less well established.6

In women with a strong familial history of BCa, with or without proven BRCA mutations, annual magnetic resonance imaging and annual mammography (concomitant or alternating) are recommended.6

The main focus of the South African clinical guidelines for BCa control and management, is to promote early detection and treatment. The guidelines state that all women irrespective of the reason for the visit to a public healthcare facility should receive provider initiated screening clinical breast examination.7

The examination should be done systematically, followed by the recording of the results. If any abnormality is detected irrespective of the severity, that woman should immediately be given a referral letter detailing the findings to the regional breast unit.7

The guidelines recommends annual mammography in women at high risk (>30%+ lifetime risk [see box 2]) of BCa from the age of 40 (or five years before the age at which a close relative was diagnosed if this calculated age is earlier than 40 years). Ultrasonography can be used for diagnostic follow-up of an abnormality seen on screening mammography. Furthermore, the guidelines recommend that screening should stop at age 70.7

The Radiological Society of South Africa and Breast Imaging Society of South Africa recommend annual screening from 40 to 70 and regular self- and clinical breast examination (CBE).4

How can we improve BCa detection?

Although BCa survival rates have increased in most developed countries, sub-Saharan Africa has the worst mortality-to-incidence ratios globally. This is partly due to the fact that 80% of women in the region present with advanced BCa as mentioned above.8

In developed countries

Systemic mammography is accepted as the gold standard for effective screening, but in resource-limited setting, mammography is not considered cost effected and it is recommended that early detection focus on downstaging through improved BCa awareness.8

According to Lince-Deroche et al, lower-cost methods of breast disease detection, which are easily available, include breast self-examination, and a CBE performed by a healthcare provider [see box 3]).9

Lince-Deroche et al recommend the following to improve BCa detection in South Africa:9

  • Incorporate breast-health education and awareness-raising, the early signs of BCa, and breast self-examination into existing health-education and outreach activities
  • Increase the number of specialist breast centres nationwide and ensure that they are staffed with multi-disciplinary teams
  • As a first step towards population-level screening, re-train primary healthcare nurses on how to perform CBE and begin screening of asymptomatic women above 35 years of age (in addition to offering screening for all symptomatic women)
  • Strengthen existing referral systems, including through facilitated patient-transport systems
  • Maximise the use of mammography and ultrasound for diagnosis by ensuring that the machines are placed in specialist breast centres with trained personnel
  • Increase support for and links to patient advocates and counsellors in communities and within specialist breast centres to ensure comprehensive, full-spectrum care
  • Establish strong monitoring and evaluation systems to track access to and utilisation of screening, diagnostic and treatment services nationwide
  • Support and lead clinical, social, and economic research on BCa and breast-disease management in the country in order to address the current dearth of available information.

Conclusion

Finestone et al  developed a model that forecasts the incidence of five of the most commonly diagnosed cancers in South Africa. The aim of the model is to estimate the true underlying burden of cancer, as opposed to diagnosed cases only.10

The team found that the incidence of all cancers has been increasing over time. In South Africa, the total number of cases almost doubled between 2019 and 2030  (about 62 000 to 121 000 incident cases). This is a result of increases in the age specific incidence rate of cancer, as well as the growth and ageing of the South African population.10

This highlights the need for increases in resources available for cancer services, as well as rapid implementation of cancer prevention strategies, to reduce the number of future cancer cases, and thereby reduce the burden on the health system, concluded Finestone et al.10

Box 1: BCa risk factors

According to ESMO the most important risk factors include:6

  • Genetic predisposition
  • Exposure to oestrogens (endogenous and exogenous, including long-term hormone replacement therapy)
  • Ionising radiation
  • Low parity
  • High breast density
  • History of atypical hyperplasia.

 

The Western-style diet, obesity and the consumption of alcohol also contribute to the rising incidence of breast cancer.6 The South African guidelines adds lack of physical exercise, use of high saturated fats in diet and high amount of sugar in diet, as well as smoking to the list of risk factors for BCa.7

Box 2: How to determine BCa risk

Risk assessment is important to determine if a woman is at average or high risk of BCa to guide counselling regarding surveillance, risk reduction, and genetic testing.5

Risk assessment should not be used to consider a woman ineligible for screening appropriate for her age. Rather, risk assessment should be used to identify women who may benefit from genetic counselling, enhanced screening such as magnetic resonance imaging screening, more frequent CBEs, or risk-reduction strategies.5

Numerous risk assessment calculators have been developed including The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (https://ccge.medschl.cam.ac.uk/boadicea/), which calculates the risk of BCa based on family history. It can also be used to calculate the probability that an individual is a BRCA gene carrier. Another options is the International Breast Cancer Intervention Study(https://ibis.ikonopedia.com/) risk assessment tool.7

The Gail model (www.cancer.gov/bcrisktool) has been validated and is widely used. It is of limited use in some women, including those younger than 35 years, those with a family history of BCa in paternal family members or in second-degree or more distantly related family members, those with family histories of non-BCa (eg ovarian and prostate) known to be associated with genetic mutations, and high-risk lesions on biopsy other than atypical hyperplasia (eg lobular carcinoma in situ).5

Box 3: Clinical breast examination

BCa usually presents as a painless lump in the breast  Other signs include a bloody or clear nipple discharge, nipple retraction, skin changes such as dimpling (orange peel) or swelling,  lumps under the arm or a scaly rash on the nipple.7

Complaints warrant a clinical breast exam. The American National Comprehensive Cancer Network screening guidelines suggest that women between 25 and 40 years old who are asymptomatic and have no special risk factors for BCa undergo a CBE every one to three years.11

Women older than age 40, women with increased risk factors for BCa, history of BCa, and/or symptomatic patients are recommended to receive more frequent CBEs.11

ACOG recommends that any screening regimen should involve a discussion of potential risks of screening with the patient. With this in mind, the group recommends offering a CBE for average-risk women aged 25 to 39 every one to three years, and an annual breast exam to women aged over 40 years.11

ACS does not recommend regular clinical CBEs for cancer screening for women in any risk group. It does state, however, that all women should pay attention to the typical appearance and texture of their breasts and report any changes to their doctor right away.11

USPSTF does not currently provide recommendations for the use of CBE in BCa screening, citing a lack of complete evidence based on available studies. However they do recommend obtaining an extended medical history for increased genetic susceptibility to BCa.11

These historical risk features include a personal history of breast cancer prior to age 50, a personal history of bilateral breast cancer, a family history of an individual with breast and ovarian cancer, a family history of at least one male member with breast cancer, multiple family members with breast cancer and Ashkenazi Jewish ancestry. Any of these historical issues noted on initial and follow-up screening assessment should be further evaluated with genetic counselling.11

References
  1. Early Detection of Breast Cancer is Vital. https://cansa.org.za/early-detection-of-breast-cancer-is-vital/
  2. Phaswana-Mafuya N, Peltzer K. Breast and Cervical Cancer Screening Prevalence and Associated Factors among Women in the South African General Population. Asian Pac J Cancer Prev, 2018.
  3. Vanderpuye V, Grover S, Hammad N, et al. An update on the management of breast cancer in Africa. Infect Agent Cancer, 2017.
  4. Lipschitz S. Screening mammography with special reference to guidelines in South Africa. S Afr J Rad, 2018.
  5. ACOG (2017). Breast Cancer Risk Assessment and Screening in Average-Risk Women. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2017/07/breast-cancer-risk-assessment-and-screening-in-average-risk-women
  6. Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Annals of Oncology, 2019.
  7. South African National Department of Health. Clinical guidelines for breast cancer control and management, 2018. https://www.cansa.org.za/files/2019/08/DOH-Breast-Cancer-Guidelines-Final.pdf
  8. Martei YM, Duada B, and Vanderpuye V. Breast Cancer Screening in sub-Saharan Africa: a systematic review and ethical appraisal. BMC Cancer, 2022.
  9. Lince-Deroche N, Rayne S, van Rensburg C, Benn C, et al. Breast cancer in South Africa: developing an affordable and achievable plan to improve detection and survival. SAHR 20th edition, 2017. https://www.hst.org.za/publications/South%20African%20Health%20Reviews/17_Breast%20cancer%20in%20South%20Africa_developing%20an%20affordable%20and%20achievable%20plan%20to%20improve%20detection%20and%20survival.pdf
  10. Finestone E and Wishnia J. Estimating the burden of cancer in South Africa. SA Journal of Oncology, 2022.
  11. Henderson JA, Duffee D, Ferguson T. Breast Examination Techniques. [Updated 2022 May 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

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