Update on the Recommendations on Breast Cancer Screening by the Cancer Expert Working Group on Cancer Prevention and Screening

Abstract

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population:

* Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening.

* A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

Introduction

In Hong Kong, the Cancer Coordinating Committee, chaired by the Secretary for Food and Health, was established in 2001 to formulate strategies regarding cancer prevention and control. The Cancer Expert Working Group on Cancer Prevention and Screening (CEWG), under the Cancer Coordinating Committee, was formed in 2002 to regularly review international and local evidence, then make local recommendations on cancer prevention and screening.

Breast cancer (BC) is the most common cancer among women in Hong Kong. Although evidence from other countries suggests that organised mammography screening is effective for detecting BC at an earlier stage and reducing mortality among affected patients, there is a lack of information concerning its usefulness and cost-effectiveness in Hong Kong. While BC risk prediction models such as the Gail model were developed in other areas for estimation of an individual's risk of BC, such models have not been validated in Hong Kong.

To address the aforementioned evidence gaps, the Hong Kong SAR Government previously commissioned The University of Hong Kong to conduct the Hong Kong Breast Cancer Study (HKBCS) for the quantification of relevant BC risk factors and development of a model for BC risk stratification among women in Hong Kong. Based on the findings of the HKBCS and other relevant studies, as well as epidemiological findings in Hong Kong and other countries, the CEWG updated its recommendations on BC screening; these updated recommendations were endorsed by the Cancer Coordinating Committee in June 2020. This article focuses primarily on the revised CEWG screening recommendations for women at average risk of BC in the general population; it also discusses the rationale for such recommendations.

Local epidemiology

In Hong Kong, 4761 invasive BC cases in women were recorded in 2019; this constituted 27.4% of all new cancer cases in women.¹ The median age at diagnosis was 58 years; 72% of patients had stage I or II BC.1 In 2020, BC was the third leading cause of cancer death in women (751 deaths).² The age-standardised incidence rate in 2019 and age-standardised mortality rate in 2020 were 70.9 and 9.7 per 100 000 world standard population, respectively.²Over the past three decades, the age-standardised incidence rate has demonstrated an upward trend while the age-standardised mortality rate did not significantly change.²

Risk factors and primary prevention

Established risk factors for BC include family history of BC, inheritance of certain gene mutations, history of radiation therapy at a young age, personal history of BC or benign breast diseases, hormonal and reproduction factors, alcohol consumption, obesity after menopause, and physical inactivity.^{3 4 5 6 7 8 9 10 11 12 13 14 15 16 17} The relative risks (RRs) associated with established risk factors for BC are summarised in Table 1.^{3 4 5 6 7 8 9 10 11 12 13 14 15}

Table 1. Relative risks associated with established risk factors for breast cancer

Primary preventive measures are important for lowering the risk of BC because some risk factors are modifiable. These preventive measures include regular physical activities, avoidance of alcohol consumption, and the maintenance of a healthy body weight and waist circumference.¹⁵ Moreover, women are recommended to extend breastfeeding and give birth at an earlier age to reduce their BC risk.^{12 15}

Breast awareness

Breast awareness refers to a woman's familiarity with the normal look and feel of her breasts, which facilitates prompt reporting of any abnormality to doctors for early diagnosis and treatment. Delayed pursuit of medical attention could lead to worse survival in patients with BC; for example, the 5-year survival rate was 7% higher among BC patients who began treatment [lesser than]3 months from symptom onset than among patients who began treatment 3 to 6 months from symptom onset.¹⁸

Screening for women in the general population

Importantly, BC screening is intended to detect BC in asymptomatic women before symptom onset; this facilitates a better treatment outcome and improves survival. Breast self-examination, clinical breast examination, and mammography are the most widely studied screening modalities for BC.

Breast self-examination and clinical breast examination

In contrast to breast awareness, breast self-examination refers to the regular and systematic self-examination of a woman's breasts. Meta-analysis and two randomised controlled trials (RCTs) in Shanghai and Russia showed that the use of breast self-examination did not produce significant differences in the size or stage of BC, or in the number of BC deaths; however, it generated false-positive findings, including more benign lesions detected and unnecessary biopsies performed.^{19 20 21} Thus, international health agencies including the International Agency for Research on Cancer (IARC), the American Cancer Society, and the US Preventive Services Task Force (USPSTF) recommend against teaching women breast self-examination as a screening modality for BC^{17 22 23 24}; these agencies encourage women to become more aware of breast changes and promptly seek medical advice regarding changes.^{17 24 25} With respect to clinical breast examination, three RCTs showed that this screening modality could detect smaller lesions and earlier stages of BC.^{26 27 28} However, there is inadequate evidence that clinical breast examination screening reduces BC mortality among asymptomatic women.^{17 21 22 23 24}

Mammography screening

Evidence from other countries suggests that organised mammography screening programmes are effective in detecting tumours at an early stage and reducing BC deaths, with the greatest benefit observed among women aged 50 to 69 years.^{17 22 23 24 29 30 31 32 33}

Mammography screening was associated with an approximately 20% reduction in BC mortality among women of all ages at average risk after 13 years of follow-up, as reported in meta-analyses of RCTs (RR=0.80-0.82), a meta-analysis of cohort studies (RR=0.75), and modelling studies (median RR=0.85).^{22 29} When compared with women aged [lesser than]50 years, mammography screening for women aged [greater than or equal to]50 years was associated with slightly greater BC mortality reduction (14%-23% vs 15%), mostly because of greater mortality reduction among women aged 60 to 69 years (31%-32%).²⁹

A systematic review by the USPSTF reported the effects of mammography screening in different age-groups. Fair-quality evidence from a meta-analysis of mammography trials showed that the RRs for BC mortality were 0.92 (95% confidence interval [CI]=0.75-1.02) among women aged 39 to 49 years, 0.86 (95% CI=0.68-0.97) among women aged 50 to 59 years, 0.67 (95% CI=0.54-0.83) among women aged 60 to 69 years, and 0.80 (95% CI=0.51-1.28) among women aged 70 to 74 years; the mortality benefit generally increased with age.³⁰ Similarly, the Canadian Task Force on Preventive Health Care reviewed the benefit of mammography screening for average-risk women aged 40 to 74 years; screening resulted in a modest reduction in BC mortality, with the lowest absolute benefit among women aged [lesser than]50 years.³³

Biennial mammography screening is recommended for some women in some developed countries such as Australia, Canada, the US, and European countries.^{24 33 34} The IARC has evaluated the effectiveness of biennial mammography screening in some of these countries; approximately 40% reduction in BC mortality was observed among women aged 50 to 69 years who had undergone screening.^{17 23} Additionally, a significant reduction in advanced BC was observed among women aged [greater than or equal to]50 years who underwent screening (RR=0.62, 95% CI=0.46-0.83), but not among women aged 39 to 49 years.³⁰

Although the benefit of using mammography as a tool for BC screening is evident, there are limitations concerning its use as a screening modality.^{17 22 23 24 29 30 31 32 33 35} Possible adverse outcomes related to such use of mammography include overdiagnosis and overtreatment. For example, women with a diagnosis of ductal carcinoma in situ often rapidly undergo radical treatment although they may live with this non-invasive condition in the absence of diagnosis and subsequent treatment. Estimates of the rate of overdiagnosis varied widely, depending on study designs and methodologies. Observational studies generally led to estimated overdiagnosis rates of 0% to 54%, while the rates estimated on the basis of RCT data ranged from 11% to 22%.^{32 35 36} A pooled analysis of 13 European studies also reported wide variation, such that crude estimates of overdiagnosis ranged from 0% to 54%; these estimates were reduced to 1% to 10% after adjustment for BC risk and lead-time bias.^{17 29}

Mammography screening could also cause false-positive findings which lead to recall for unnecessary, additional imaging and subsequent invasive procedures (mostly biopsies). The USPSTF systematic review of mammography screening revealed that the 10-year cumulative false-positive and biopsy rates were higher for annual screening than for biennial screening (61% vs 42% and 7% vs 5%, respectively); these rates were also higher among women aged 40 to 49 years and women with dense breasts.³⁵ The IARC Working Group estimated that the cumulative risk of false-positive recall in organised screening programmes was approximately 20% for women who underwent mammography screening 10 times between the ages of 50 and 70 years, where fewer than 5% of all false-positive mammography screening results led to an invasive procedure.^{17 23} Women may experience anxiety while waiting for the results of mammography screening or upon recall for further investigations. Women with false-positive mammography results generally experienced short-term negative psychological consequences, although such effects could be mitigated via clear communication with their physicians.^{17 23 25}

Radiation-induced BC is also a concern for women. Systematic reviews estimated that the risk of death from mammography-related radiation-induced BC ranged from 1 to 11 per 100 000 women, depending on age and screening interval; however, such risk is outweighed by the ability of mammography to prevent BC deaths.^{17 23 35}

Concerning the frequency of mammography screening, no RCTs have directly compared the benefits of annual to biennial screening in women of any age; however, observational studies found no differences between biennial and annual screening in women aged [greater than]=50 years.^{24 29 30} A modelling study from the US estimated that women screened biennially from age 50 to age 74 avoided a median of seven BC deaths versus no screening, whereas women screened annually from age 40 to age 74 avoided additional three deaths; however, annual screening yielded 1988 more false-positives and 11 more overdiagnoses per 1000 women screened, indicating that biennial screening is a more cost-effective strategy for average-risk populations of women.³⁷ Guidelines from other regions (eg, the World Health Organization, USPSTF, and most developed countries) generally recommend biennial mammography screening for women at average risk of BC.^{24 34 38}

Previously, the CEWG considered the available scientific evidence to be insufficient for recommendations regarding population-based mammography screening among women at average risk in Hong Kong. Recently, the University of Hong Kong research team completed a territory-wide case-control study (HKBCS) involving 3501 BC cases and 3610 controls.³⁹ The study estimated the risk of BC in women based on a list of parameters including age, age at menarche, age at first live birth, family history of BC among first-degree relatives, prior benign breast disease diagnosis, body mass index, and physical activity (Table 2).³⁹ The RRs of these identifiable risk factors were incorporated to develop a risk prediction model (ie, personalised risk assessment tool) applicable to the Chinese population in Hong Kong, with the aim of guiding mammography screening and improving the cost-effectiveness of mass screening. The HKBCS found that while the relative reduction in BC mortality was similar between risk-based screening and conventional age-based screening, it would be more cost-effective to provide risk-based biennial mammography screening to Hong Kong Chinese women aged 44 to 69 years who had an increased risk of BC according to the newly developed risk assessment tool.³⁹ Targeted screening in women at increased risk of BC would reduce the potential for harm related to unnecessary biopsy or other invasive tests conducted to confirm false-positive mammography findings; it would also optimise the use of scarce healthcare resources. Women with high risk (eg, BRCA1/2 mutation carriers) and moderate risk, as defined by the CEWG, should follow the respective CEWG recommendations on BC screening (Table 3).⁴⁰

Table 2. Relative hazards in Hong Kong (2016-2019)39

Table 3. Revised CEWG recommendations on breast cancer screening40

Other imaging techniques

Compared with conventional two-dimensional mammography, digital breast tomosynthesis (also known as three-dimensional mammography) lowers recall rates for false-positives and detects more cancers; however, it exposes women to more radiation.^{17 23 24 30 41 42} Thus far, it remains unclear whether digital breast tomosynthesis can provide to patients by detecting clinically significant cancers, rather than causing overdiagnosis. Current international guidelines do not support the use of digital breast tomosynthesis as a screening tool and future research in this area is warranted.^{17 23 24 30 33}Ultrasonography, as an adjunct to mammography in women with radiologically dense breasts, may depict small BCs not visible on mammography, while increasing false-positive recall.^{43 44} Systematic reviews conducted by Cochrane, IARC, and USPSTF have concluded that there is insufficient evidence to support the use of ultrasonography in asymptomatic women as a routine screening tool to decrease BC mortality.^{17 23 24 25}

Revised recommendation

In accordance with local data and the latest scientific evidence, the CEWG has revised its BC screening recommendations for women in Hong Kong, as summarised below⁴⁰:

1. Breast self-examination is not recommended as a screening tool for BC for asymptomatic women. Women are recommended to be breast aware (be familiar with the normal look and feel of their breasts) and seek medical attention promptly if suspicious symptoms arise.

2. There is insufficient evidence to recommend clinical breast examination or ultrasonography as a screening tool for BC for asymptomatic women.

3. It is recommended that risk-based approach should be adopted for BC screening.

4. While the BC screening recommendations for (a) women at high risk remain status quo, those for (b) women at moderate risk and (c) other women at general population are revised. Details of recommendations for women at different risk profiles are listed in Table 3.⁴⁰

Author contributions

All authors have made substantial contributions to the concept or design, acquisition of data, analysis or interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

Conflicts of interest

As editors of this journal, DVK Chao, HHF Loong, and MCS Wong were not involved in the peer review process of this article. The other authors have no conflicts of interest to disclose.

Declaration

An earlier version of this article was published online at the website of the Centre for Health Protection in January 2021: Cancer Expert Working Group on Cancer Prevention and Screening (CEWG). Recommendations on Prevention and Screening for Breast Cancer[-]For Health Professionals. Centre for Health Protection; January 2021. https://www.chp.gov.hk/ files/pdf/breast_cancer_professional_hp.pdf

Funding/support

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors

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