Screening and Pathogenesis

Question

Describe the principles, evidence and public health impact of mass screening for breast cancer, with particular reference to digital mammography and breast density assessment.

Principles

• Aim: detect clinically occult cancer earlier to reduce mortality.

• Requires:

  • significant disease burden

  • detectable preclinical phase

  • effective screening test

  • effective diagnostic and treatment pathway

  • acceptable benefits vs harms/cost.

• Screening is for asymptomatic women; symptomatic women require diagnostic assessment.

Digital mammography

• Cornerstone of population breast screening.

• Detects masses, architectural distortion and microcalcifications/DCIS.

• BreastScreen Australia: 2-yearly screening, targeting women 50–74 years.

• Digital breast tomosynthesis (DBT/3D mammography) reduces tissue overlap and can increase cancer detection, particularly in dense breasts.

Australian statistics — numbers to remember

• 1.95 million women aged 50–74 screened in 2023–24.

• 52.3% participation.

• 6,410 invasive cancers detected in women aged 50–74 in 2023.

• 57.8% of screen-detected invasive cancers were ≤15 mm.

• Recall rate: 10.6% first screen vs 3.8% subsequent screens.

• 2-year program sensitivity: approximately 78%.

• Breast cancer mortality in women aged 50–74 fell from 74/100,000 in 1991 to 37/100,000 in 2023 — approximately a 50% reduction. This reflects screening plus improvements in treatment, so cannot be attributed to screening alone.

Breast density

• Mammographic density is:

  • an independent breast cancer risk factor

  • a masking factor, reducing mammographic sensitivity.

• BI-RADS density:

  • A: almost entirely fatty

  • B: scattered fibroglandular

  • C: heterogeneously dense

  • D: extremely dense

• C and D = dense breasts.

• Dense breasts increase the risk of interval cancer and reduce mammographic sensitivity.

• Density should be incorporated into individual risk assessment.

• Dense breasts alone do not automatically mandate additional imaging.

• Supplemental ultrasound, DBT, MRI or contrast-enhanced mammography may be considered according to overall risk and clinical circumstances.

Benefits

• Earlier diagnosis

• More small, potentially curable cancers detected

• Reduced breast cancer mortality

• Potentially less extensive treatment.

Harms / limitations

• False positives and additional imaging/biopsy

• False-negative/interval cancers

• Overdiagnosis and overtreatment

• Radiation exposure

• Reduced sensitivity in dense breasts

• Participation and access inequities.

Public health impact

Participation → early detection → diagnosis → effective treatment → improved outcomes

• Population screening has contributed to earlier diagnosis and reduced breast cancer mortality.

• However, detecting more cancers is not the same as reducing mortality; overdiagnosis and overtreatment must be considered.

• High participation and equitable access to assessment and treatment are essential.

Exam take-home point

Digital mammography remains the cornerstone of population screening. Breast density is both a risk factor and a cause of masking. The objective is not simply to detect more cancers, but to detect clinically significant cancers early enough to improve outcomes.

Key Australian resources

• AIHW — BreastScreen Australia Monitoring Report 2025: participation, detection, sensitivity, interval cancers and mortality.

• Cancer Council Australia — Breast Cancer Screening: mammography, DBT and supplemental imaging.

• BreastScreen Australia — Position Statement on Breast Density and Screening

• Cancer Australia — Breast Cancer Optimal Care Pathway

• Australian Government Department of Health and Aged Care — BreastScreen Australia

1. Diagnostic work-up

• Clinical: bilateral breast and nodal examination; document tumour size, skin/nipple involvement, performance status and comorbidities.

• Imaging: bilateral diagnostic mammography ± tomosynthesis + targeted breast/axillary ultrasound.

• MRI: if extent is uncertain, multifocal/multicentric disease suspected or for surgical planning.

• Pathology: confirm invasive carcinoma, grade, ER, PR, HER2 ± Ki-67.

• Axilla: ultrasound; core biopsy/FNA of suspicious node if it will alter management. Clip biopsy-proven nodes if neoadjuvant therapy is planned.

• Stage: clinically cT2N1 if no distant disease. CT chest/abdomen/pelvis ± bone imaging/PET-CT according to stage, symptoms and local protocol.

• MDT: discuss at breast MDM.

• Consider genetic testing, fertility/pregnancy issues and genomic testing where results will influence systemic therapy.

2. Primary surgery vs neoadjuvant systemic therapy

Primary surgery — FOR

• Operable disease with no distant metastases.

• Breast conservation may be feasible.

• Provides definitive tumour and nodal pathology.

• Particularly reasonable in HR+/HER2− disease where neoadjuvant chemotherapy is less likely to achieve pCR.

Neoadjuvant therapy — FOR

• Downstages breast and axilla.

• May increase breast-conservation rates.

• Allows assessment of treatment response.

• May reduce extent of breast/axillary surgery.

• Appropriate when systemic therapy is indicated regardless of surgery.

Strongest indications: locally advanced, inflammatory, large operable, triple-negative or HER2-positive breast cancers.

In this patient

• HR+/HER2−, cT2N1 → primary surgery is a reasonable option if technically resectable.

• Neoadjuvant chemotherapy may be considered if:

  • breast conservation is otherwise difficult

  • significant nodal disease is confirmed

  • tumour biology/clinical risk warrants chemotherapy

  • downstaging would alter surgical management.

• Neoadjuvant endocrine therapy is less established in premenopausal women and is not a routine substitute for chemotherapy in a fit, node-positive patient.

• Final decision should be through MDM + shared decision-making.

EXAM take-home

Triple assessment → assess/biopsy axilla → stage → MDM → decide whether systemic therapy should precede surgery.

For HR+/HER2− cT2N1 disease, primary surgery is reasonable, while neoadjuvant therapy is mainly considered when downstaging or systemic treatment is expected to change management.

Australian references

• Cancer Council Australia – Breast Cancer Optimal Care Pathway, 2nd ed.

• Cancer Council Australia – Breast Cancer Treatment Guidelines

• eviQ – Breast cancer neoadjuvant/adjuvant systemic therapy protocols

• Cancer Council Australia – Guide to Best Cancer Care: Breast Cancer

• Cancer Australia – Breast Cancer

1. SLNB vs ALND

• SLNB is standard axillary staging for clinically node-negative invasive breast cancer.

  • Minimally invasive with lower morbidity.

  • If negative → no further axillary surgery in most patients.

• ALND provides greater nodal clearance but has significantly greater morbidity:

  • lymphoedema

  • shoulder dysfunction

  • sensory disturbance/axillary web syndrome.

• ALND remains appropriate for selected patients with significant nodal disease, depending on upfront vs neoadjuvant treatment and radiotherapy.

2. ACOSOG Z0011

Key trial: 891 patients with:

• T1–T2 invasive breast cancer

• clinically node-negative

• 1–2 positive SLNs

• breast-conserving surgery

• whole-breast radiotherapy

• systemic therapy.

Results at 10 years:

• Overall survival: 86.3% SLNB alone vs 83.6% ALND

• Disease-free survival: 80.2% vs 78.2%

• No significant difference in regional recurrence.

Clinical implication:

Do not routinely perform ALND for 1–2 positive SLNs in a Z0011-eligible patient undergoing breast-conserving surgery and appropriate adjuvant therapy.

Important limitations: Z0011 does not automatically apply to:

• mastectomy

• 2 positive SLNs

• clinically palpable/significant nodal disease

• patients outside the trial population.

3. Targeted Axillary Dissection (TAD)

Particularly relevant for biopsy-proven node-positive patients receiving neoadjuvant systemic therapy.

• Before neoadjuvant therapy: biopsy and clip the positive node.

• At surgery: remove:

  • the clipped/target node +

  • sentinel lymph nodes.

• This is TAD and improves identification of residual nodal disease.

Key statistics:

• SLNB alone after neoadjuvant therapy: FNR approximately 10.1% in the Caudle study.

• Adding removal of the clipped node reduced FNR to 1.4%.

• The clipped node was not an SLN in 23%, demonstrating why targeted removal matters.

• Initial TAD series reported FNR of approximately 2%.

EXAM take-home

Clinically node-negative → SLNB

1–2 positive SLNs + Z0011 criteria → usually no ALND

Biopsy-proven node-positive → neoadjuvant therapy → clip node → TAD ± further axillary treatment according to residual disease

The modern principle is axillary de-escalation without compromising oncological outcomes.

Australian references

• Cancer Australia – Surgery to the Axilla

• Cancer Council Australia – Surgery for Breast Cancer

• Giuliano et al. – ACOSOG Z0011, JAMA 2017

• Caudle et al. – Targeted Axillary Dissection, JCO 2016

• eviQ – Adjuvant nodal irradiation / Z0011 evidence