Further Readings

Natural History and Risk Factors for Breast Cancer

• There are 2 types of breast cancer: ductal carcinoma in situ (DCIS) and invasive breast cancer. DCIS consists of presumably malignant cells confined to the mammary ducts and is considered a precursor to invasive breast cancer, with 10-53% of cases progressing to invasive forms.^9-12 Invasive breast cancer consists of cancer cells that have invaded surrounding tissues. It can be further divided into histological subtypes, with invasive ductal carcinoma being the most common, followed by invasive lobular carcinoma.^{9, 13} Molecular subtypes include Luminal A, Luminal B, basal-like, and HER2-enriched, each associated with different treatment responses and prognoses. The basal-like and triple-negative subtypes (lacking estrogen receptors, progesterone receptors, and absence of HER2 overexpression) have poorer prognoses; Individuals with BRCA-1 mutations have a higher risk of these subtypes.^14-16 Risk factors for breast cancer were listed in S Table 1.
• Breast cancer may not always present as a palpable lump in its early stages, particularly in cases of DCIS. When tumors become large enough to be felt, they often indicate a later stage of the disease. Without breast cancer screening, 83% of breast cancer patients presented with a painless lump, 6.8% presented with nipple abnormalities, 6.4% presented with breast pain, 2% presented with breast skin abnormalities, 1.2% presented with axillary lump, 0.6-0.7% presented with breast contour abnormalities or inflammation.¹⁷ Both screening and early diagnosis facilitated disease detection at earlier stages and improve survival outcomes.¹⁸

Effectiveness of Breast Cancer Screening²

• Mammography (MMG) screening allows disease detection at an asymptomatic stage and improves survival outcomes. For women aged 39-49 at average risk, breast cancer screening is associated with a relative risk (RR) of 0.92 (95% CI 0.75-1.02) in breast cancer mortality compared to those without screening over 10 years of follow-up.³ For women aged 50-59, the RR was 0.86 (95% CI 0.68-0.97); for those aged 60-69, the RR was 0.67 (95% CI 0.54-0.83); and for ages 70-74, the RR was 0.80 (95% CI 0.51-1.28). Additionally, women aged 50-69 who participated in organised mammography screening were found to have approximately 40% reduction in the risk of breast cancer mortality.¹⁹ Screening for women under 30 is not recommended due to increased false positive results and risk of over-diagnosis in this younger age group.²⁰
• Clinical breast examination is no longer recommended for breast cancer screening due to insufficient evidence regarding its effectiveness in reducing breast cancer mortality,²¹ with reported sensitivity of 54.1% (95% CI: 48.3%-59.8%), specificity of 94.0% (95% CI: 90.2%-96.9%), positive predictive value of 14% (95% CI, 2‒43%) and negative predictive value 92% (95% CI, 89‒94%).^{22, 23} Similarly, self-breast examinations are also discouraged because of potential harms related to false positives and unnecessary biopsies.^{24, 25} The sensitivity of self-breast examinations ranged from 20% to 30%, while their specificity was 87.4%.²⁶
• Risk-based biennial mammography screening was found to be cost-effective in reducing the lifetime risk of breast cancer mortality for women aged 44 to 69 in Hong Kong. A local study estimated that risk-based screening among average-risk women in Hong Kong could yield a health gain of 0.009 quality-adjusted life years (QALY) at a net cost of $159 per woman, resulting in an incremental cost-effectiveness ratio of $18,151 per QALY.²⁷ Personalized risk-based screening for breast cancer was demonstrated to be more cost-effective than universal age-based screening in Chinese women with average risk. This contrasts with recommendations from other countries, such as the United Kingdom, Australia, and Singapore, which offer universal screening for all women starting at age 50.
• Recommendations for breast cancer screening for high- and moderate-risk women were made by the CEWG based on evidence from international studies and practices. Studies have shown that MRI screening in high-risk women significantly shifted cancer diagnosis from advanced stages to earlier and pre-invasive stages compared to other screening modalities, such as mammography (MMG), and ultrasonography. The International Agency for Research on Cancer (IARC) concluded that MRI, when used as an adjunct to mammography (MMG), could increase sensitivity and decrease specificity in screening women with a high familial risk and BRCA1/2 mutation.^{19, 28} Therefore, individual screening strategies for high risk individual should take into consideration the increased risk of false positive results associated with adjunctive MRI.
• Adjunctive MRI is not recommended for breast cancer screening of women with moderate risk due to risk of false positive results and reduced-cost-effectiveness.^{19, 28-31} Adjunctive ultrasound to MMG for breast cancer screening in women with radiologically dense breasts could enhance cancer detection sensitivity.³² However, the accuracy of breast ultrasound is operator-dependent, and its use alongside MMG has been associated with an increased rate of false positives and unnecessary biopsies compared to MMG alone.^{19, 33, 34} Breast cancer screening with ultrasound alone is not recommended due to higher risk of false positive results compared to MMG alone.³⁵
• The performances, advantages and limitations of different breast cancer screening methods were summarized in S Table 2.

Interventions to Promote Uptake of Breast Cancer Screening

• Despite the benefit of breast cancer screening, the uptake rate of mammography screening is yet to be optimised. Barriers for individuals to undergo mammography included: (1) they do not see the need for screening as they are asymptomatic and healthy; (2) they were never recommended to undergo screening by healthcare professionals; (3) cost for mammography is too high; (4) low health literacy with lack of knowledge on the importance of breast cancer screening.^{36, 37} Community-based health education interventions promoting breast cancer screening through newspapers, exhibitions, lectures, information stalls, posters were demonstrated to be effective in encouraging mammography uptake (OR = 3.14, 95% CI 1.98 - 5.01).³⁸ Campaign on raising medical professional awareness on breast cancer screening may be relevant in near future to encourage referral of eligible individuals to breast cancer screening.