🧑‍🦰👨‍🦰Locally Advanced Breast Cancer + Male Breast Cancer

Question 1

What is Locally Advanced Breast ca. ?

Answer 1

Cancer that has not spread beyond breast or other parts of the body.

This includes:

• Large breast tumors (>5 cm in diameter)
• Cancers that involve skin of breast or underlying chest wall muscles
• Cancers that involve multiple ipsilateral axillary, internal mammary or infra/supra-clavicular lymph nodes
• Inflammatory breast cancer

Stage IIB (T3 N0 M0)

Stage IIIA (T0-3 N2 M0, T3 N1 M0)

Stage IIIB (T4 N0-2 M0)

Stage IIIC (T Any N3 M0)

Question 2

Overview of Locally Advanced Breast Cancer management

Answer 2

Question 3

Role of Neoadjuvant Chemotherapy in Locally Advannced Breast ca.

Answer 3

Indicated in women with inoperable breast cancer. It can render inoperable cancer to resectable or increase rate of BCS and benefits in operable breast cancer with BCS intention.

Definition of inoperable disease [NCCN]

• IBC
• Bulky or matted cN2 axillary nodes
• cN3 nodal disease
• cT4 tumors

Question 4

Primary Breast surgery ( BCS / Mastectomy)

Answer 4

• No difference in LR and regional recurrence between BCS and mastectomy in LABC with good response to neoadjuvant chemotherapy (NACT).
• However the DFS (OR=2.35 95% CI 1.84 to 3.01) and OS (OR=2.12 95% CI 1.51 to 2.98) were shown to be higher in BCS. [DOI:10.1097/MD.0000000000008367]
• Surgery timing - 1 month after PST.
• Patient on ET continue treatment during perioperative period
• Re-testing post-surgery HPE for ER/PR & HER2 status not advisable due to possible discordance.
• Surgical margin follows post neoadjuvant tumor size.
• Tissue orientation must be properly marked, and pathologist informed of post adjuvant specimen.

Question 5

Adjuvant Therapy post primary Breast surgery

Answer 5

RT

• BCS : WBRT + RT booster to chest wall + Regional RT
• Mastectomy : Chest wall + Regional RT (if LN positive)

CT - considered in patient with:

• Triple - ve who did not complete both combined Taxane & Anthracycline adjuvant therapy.
• Patient treated with adjuvant ET
• Patient did not complete planned adjuvant therapy

HER2 - HER2 +ve patients (Continue for 1 year)

ET - For 10 years

Question 6

SENTINA TRIAL

Answer 6

🎯 Key Clinical Impacts of the SENTINA Trial

1️⃣ Timing of Sentinel Lymph Node Biopsy (SLNB)
✅ SLNB before NACT is more reliable in clinically node-negative (cN0) patients

Low false-negative rate (FNR: 8.6%)
High detection rate (99.1%)
🚫 SLNB after NACT in previously node-positive patients (converted to node-negative) is less reliable

FNR increases to 14.2% (Arm C)
If repeat SLNB (Arm B), FNR jumps to 51.6%
📌 Impact:
→ Encouraged clinicians to consider SLNB before NACT for accurate axillary staging
→ Raised concerns about the reliability of post-NACT SLNB in initially node-positive patients

🧠 Summary:
* ✅ Arm A has the lowest FNR → SLNB before NACT is most reliable
* ❌ Arm B has the highest FNR (51.6%) → repeat SLNB after NACT is unreliable
* ⚠️ Arm C has moderate FNR (14.2%) → SLNB post-NACT in downstaged cN+ patients has limited accuracy
* ⛔ Arm D → No SLNB done, so FNR is not applicable

Question 7

🧔‍♂️ Male Breast Cancer (MBC) — Key Points

Answer 7

📊 Epidemiology
<1% of all breast cancers, <1% of all cancers in men.
Incidence rising until ~2000, then plateaued.
Common in North America, Europe; higher rates in sub-Saharan Africa (e.g. 6% in Tanzania).

🧫 Pathology
- 90% invasive: majority ductal (90%), papillary (2%), lobular (1%).
- 10% non-invasive, mostly DCIS.
- ER-positive in ~92% of men (vs 78% in women).
- HER2, p53, and other markers: data limited and inconclusive.

🧬 Risk Factors
- Hormonal imbalance: ↑ estrogen, ↓ testosterone.
- Causes: Klinefelter’s syndrome (47XXY), obesity, cirrhosis, undescended testes, infertility.
- Genetics:
Family history: ↑ risk 2x (1st-degree relative), 10x (mother + sister).
Genes: BRCA2 (5–10% lifetime risk), BRCA1 (1–5%), PTEN, P53, CHEK2.

• Others:
  Obesity, diabetes, never fathered children, prior radiation.

Not linked: alcohol, gynaecomastia (no longer considered a risk).

🩺 Clinical Presentation
Median age: 67 years.
- Most common: painless central breast mass (50–97%).
- Other signs: nipple retraction, discharge, pain, ulceration.
- Diagnosis delay: 6–21 months → later-stage presentation.

🔍 Diagnosis
DDx: gynaecomastia, carcinoma, abscess, sarcoma.
- Workup: Physical exam → mammogram + US → core-needle biopsy.
- Mastectomy is mainstay, so imaging plays minor role unless BCS is planned.

🛠️ Treatment
🏥 Local Therapy
- Mastectomy is preferred (central tumors, little breast tissue).
- BCS in ~17% of cases; if done, only ~46% get adjuvant RT.
- Radical mastectomy no longer indicated.
- Axillary staging: SLNB if clinically/radiologically negative; otherwise core biopsy or FNA.

💊 Adjuvant Therapy
Same as female breast cancer.
- Tamoxifen: standard for ER+ tumors.
- Aromatase inhibitors: only with orchiectomy due to testicular feedback loop.

🎯 Metastatic Disease

• ER+ → endocrine therapy (tamoxifen preferred).
• ER− → chemotherapy.
• Older options: orchiectomy, progestins, estrogens, anti-androgens.

📉 Prognosis
- Similar stage-for-stage prognosis as women.
- Prognostic factors: Nodal status, tumor size/grade, hormone receptor, HER2.
- 5-year survival:
Node-negative: 95%
1–3 nodes: 87%
≥4 nodes: 80%

• ER+/PR+ tumors → better survival than ER−/PR−.
• Improvements in survival over decades, though more modest in men vs women.