Breast Cancer

Screening (American Cancer Society):

• Average Risk:

  • 40 - 44 years old: have the option to start screening with a mammogram every year.

  • 45 - 54 years old: should get mammograms every year.

  • 55 and older:

    • Can switch to a mammogram every other year, or they can choose to continue yearly mammograms.

    • Screening should continue as long as a woman is in good health and is expected to live at least 10 more years.

• High Risk:

  • Definition:

    • Women with lifetime risk of breast cancer of 20% or higher

    • BRCA1 or 2 mutation

    • First degree relative with BRCA 1/2 mutation and patient has not had genetic testing themselves

    • RT to chest before 30 years old

    • Have Li-Fraumeni Syndrome, Cowden Syndrome, Bannayan-Riley-Ruvalcaba syndrome

  • 30 and older: Breast MRI and mammogram every year

    • No mammogram for women younger than 30

• Indications for screening with Breast MRI:

  • High-risk women (mentioned above) with age 30 and older

  • Women with history of breast cancer who were diagnosed at age 50 or less

  • Women with history of breast cancer and have dense breasts

    
    

Workup:

• Diagnostic bilateral mammogram

• Ultrasound as necessary

• Suspicious examination but negative mammogram

• Biopsy of suspicious lesion (core biopsy preferred)

  • ER/PR/HER2 status

  • Ki67 status

  • Grading

• Systemic imaging for patients with clinical stage I - III breast cancer should be performed largely based on whether patient has concerning signs/symptoms suggestive of having metastatic disease

• Breast MRI may be helpful if:

  • Breast cancer evaluation before and after preoperative systemic therapy to define extent of disease

  • Identifying primary cancer in women with axillary nodal adenocarcinoma or occult primary cancer, with Paget’s disease, or invasive lobular carcinoma poorly defined on mammography, ultrasound or physical exam

  • Staging evaluation to define extent of cancer or presence of multifocal/multicentric cancer in the ipsilateral breast

  • Screening for contralateral breast at time of initial diagnosis

• Defining menopause: 12 months or more of amenorrhea

  • Need to establish menopause status in women age < 60 at the beginning of chemotherapy to decide on endocrine regimen

High Risk/Non-Malignant Breast Lesions

• Types:

  • Lobular Carcinoma In Situ (LCIS)

  • Atypical Ductal Hyperplasia (ADH)

• 15-30% chance of progression to invasive breast cancer

• If noted on biopsy, should be excised to rule out any invasive component

• Require breast examination q4-12 months

• Treatment:

  • Surgery + ET (Tamoxifen if premenopause, Aromatase inhibitor if postmenopause)

Ductal Carcinoma In Situ (DCIS)

• DCIS: non-invasive stage 0 breast cancer

• Treatment of LCIS and DCIS are similar.

• No need for PET or CT scan.

• Axillary LN evaluation and HER2 test are not recommended.

• Options for treatment: 

  • Breast conserving surgery without LN surgery

    • Lumpectomy → radiation therapy (RT)

    • If HR+: Consider endocrine therapy (ET) x5 years

  • Total mastectomy + sentinel LN biopsy (in case there is an invasive component)

    • No need for adjuvant RT or ET

    • No ET is indicated.

  • Lumpectomy → Adjuvant ET x5 years + RT x5 years

    • Endocrine therapy (ET):

      • Premenopause: Tamoxifen 5 mg/day x3 years

      • Postmenopause: Raloxifen, Aromatase inhibitor

• Surgery goal is 2 mm margin upon resection.

• Trastuzumab and chemo play no role as adjuvant treatment for DCIS.

HR+ HER2- Breast Cancer

HR+ is defined as ER and/or PR ≥ 1%

Localized HR+ Breast Cancer: 

• Neoadjuvant chemo:

  • Indications:

    • Inoperable breast cancer:

      • Inflammatory breast cancer

      • bulky or matted cN2 axillary nodes (>4 LN+)

      • cN3 nodal disease

      • cT4 tumors

    • Operable breast cancer:

      • large primary tumor relative to breast size in patient who desires breast conservation

      • cN+ disease (likely to become cN0 with neoadjuvant chemo)

  • Options for HR+ neoadjuvant chemo: 

    • ddAC-T (Dose-dense Doxorubicin and Dose-dense Cyclophosphamide + Paclitaxel)

    • TC x4-6 (Docetaxel + Cyclophosphamide)

• Mastectomy (generally without adjuvant RT)

  • RT is recommended in:

    • Tumor > 5cm

    • Inflammatory breast cancer

    • Positive axillary LN+

    • If positive margins but re-excision is not possible

• Lumpectomy + RT

  • Contraindications: (they require mastectomy)

    • Inflammatory breast cancer

    • Multifocal or multi centric disease

    • Diffuse microcalcifications on mammogram

    • Positive pathologic margin

    • Pregnancy that cannot be completed or terminated before RT delivery

  • Relative contraindication: previous RT to breast/chest

  • RT can be deferred if:

    • >70 yo AND Stage pT1, cN0 AND ER+/HER2- AND ET is planned

    • > 65 yo AND Stage pN0, pT AND < 3cm AND ER+/HER2- AND ET is planned

• Sentinel LN Biopsy (SLNB) or Axillary LN dissection (ALND)?

  • ALND may be safely omitted if clinically LN- disease who are found to have 1-2 positive SLNs

• Adjuvant chemo:

  • Usually TC x4-8 cycles

  • Consider Oncotype in HR+ HER2- localized breast cancer if T1b or higher (tumor size >5 mm)

  • Indications to use Oncotype first:

    • All LN- breast cancer (TAILORx)

    • Postmenopausal with 1-3 LN+ (RxPonder)

  • Oncotype Dx Recurrence Score:

    • ≤15 (low risk):

      • No chemo

    • 16-25 (intermediate risk):

      • If >50 yo: No chemo

      • If ≤50 yo: May consider chemo + ET (TAILORx)

    • ≥ 26 (high risk):

      • chemo + ET

• Adjuvant ET:

  • Premenopausal: Tamoxifen

    • Side effects: DVT/PE, lower risk of osteoporosis, endometrial cancer (50+), hot flashes. 

  • Postmenopausal: Aromatase inhibitor

    • Side effects: hot flashes, joint pains, osteoporosis

  • Consider Breast Cancer Index at 5 years to determine 5 vs 10 years adjuvant ET

• Adjuvant Ovarian Function Suppression (OFS) x2 years: 

  • For higher risk patients (LN+ patients, patients needing chemo) can add OFS (Goserelin, Lupron) x2 years

  • Based on SOFT and TEXT trials

• Adjuvant CDK 4/6:

  • For higher risk, ER+ HER2- LN+ breast cancer:

    • >4+ LN

    • 1-3 LN with one of following:

      • Ki-67>20%

      • Grade 3 disease

      • tumor size >5 cm (T3)

  • Abemaciclib x2 years (MonarchE)

    • Side effects: Diarrhea, neutropenia

  • Ribociclib x3 years (NATALEE)

  • Palbociclib

• Adjuvant PARP inhibitor:

  • Olaparib (OlympiA)

Metastatic HR+ Breast Cancer:

• First line:

  • CDK4/6 inhibitor + AI

    • Abemaciclib (MONARCH-3)

    • Ribociclib (MONALEESA)

    • Palbociclib (PALOMA-2: Palbociclib improved PFS but not OS)

  • CDK4/6 inhibitor + fulvestrant

• Subsequent lines:

  • CDK4/6 inhibitor + fulvestrant (Switch to another CDK 4/6 inhibitor)

  • Everolimus + ET

  • Alpelisib + Fulvestrant (If PIK3CA mutated)

  • Capivasertib + Fulvestrant (if PIK3CA or AKT1 mutations or PTEN alteration)

  • PARP inhibitor (If BRCA 1/2 mutation)

  • Fam-trastuzumab deruxtecan (Enhertu)

  • Sacituzumab govetican

  • Datopotamab deruxtecan

  • Elacestrant (if ESR1 mutated)

  • Larotrectinib, entrectinib, or repotrectinib (if NTRK fusion)

  • Pembrolizumab (if TMB-H [>10 mut/Mb], MSI-H/dMMR)

  • Dostarlimab (if MSI-H/dMMR)

  • Selpercatinib (if RET-fusion)

  • Abemaciclib (only CDK4/6 inhibitor that can be used as monotherapy)

  • Single agent systemic chemotherapy (capecitabine, doxil, taxol)

HER2+ Breast Cancer

HER2+ is defined as HER2 3+ in IHC or FISH ratio >2

Localized HER2+ Breast Cancer:

• Neoadjuvant chemotherapy:

  • Indications: >2 cm (T2), LN+

  • TCHP x6 cycles

    • TCHP: Docetaxel + Carboplatin + Trastuzumab (Herceptin) + Pertuzumab

• Adjuvant chemotherapy:

  • If pCR after neoadjuvant chemo AND HR-:

    • complete HP x1 year

  • If pCR after neoadjuvant chemo AND HR+:

    • complete HP x1 year + ET x5-10 years

  • If residual disease after neoadjuvant chemo:

    • adjuvant trastuzumab emtansine/TDM-1 x14 cycles or 1 year (KATHERINE)

    • adjuvant trastuzumab emtansine/TDM-1→ Neratinib x1 year

      • If HR+ HER2+ breast cancer with a perceived high risk of recurrence

  • If did not receive neoadjuvant chemo :

    • TH x1 year

  • If N+ prior to treatment: will require adjuvant RT

Metastatic HER2+ Breast Cancer:

• First Line

  • THP (CLEOPATRA)

    • if chemo is stopped at some point, can add ET to HP (if HR+)

  • HP + Eribulin (EMERALD)

  • ET +/- HER2 targeted therapy

    • Generally for patients not candidates for chemotherapy

    • +/- lapatinib (restores/enhances sensitivity to endocrine agents)

• Subsequent Lines

  • Enhertu

  • Enhertu → T-DM1

  • Tucatinib + Capecitabine + Trastuzumab

    • Consider in patients with brain mets (HER2CLIMB)

  • Neratinib + Capecitabine

  • Lapatinib + Trastuzumab +/- Capecitabine

  • Margetuximab-ckmb + chemo (Capecitabine, Gemcitabine, Eribulin, Vinorelbine)

Triple Negative Breast Cancer (TNBC)

Needs NGS for multiple high penetrance cancer susceptibility genes

• Associated with BRCA 1/2 mutations

• Also check for CDH1, PALB2, PTEN, STK11, and TP53

  
  

Non-metastatic disease:

• Neoadjuvant chemotherapy:

  • Indications: >2 cm (T1c) or LN+

  • Treatment: Platinum based chemo + IO

  • Neoadjuvant Pembrolizumab + Carboplatin + Paclitaxel → Pembrolizumab + Cyclophosphamide + Doxorubicin → Adjuvant pembrolizumab to complete 1 year (Keynote-522)

• Adjuvant chemotherapy:

  • If pCR:

    • continue adjuvant pembro to complete 1 year (Keynote-522)

  • If residual disease after neoadjuvant chemo:

    • Adjuvant capecitabine (CREATE-X)

  • If residual disease after neoadjuvant chemo + BRCA 1/2 mutation:

    • Adjuvant Olaparib (OlympiA)

  • If did not receive neoadjuvant chemo:

    • Adjuvant ddAC-T or TC

Metastatic disease:

• Must check PD-L1 CPS score

• First line:

  • Single agent chemo: Taxanes (Paclitaxel, Docetaxel, Nab-paclitaxel), Eribulin, Anthracyclines, Capecitabine, Ixabepilone, platinums, Gemcitabine, Vinorelbine

  • If PD-L1 CPS<10 + visceral crisis: Consider ddAC-T

  • If PD-L1 CPS>10: Chemo + Pembrolizumab (Keynote-355)

• Subsequent lines:

  • Sacituzumab govitecan (ASCENT)

    • Black Box Warning: Diarrhea and Neutropenia

    • Needs 2 prior lines of therapy

  • If BRCA mutation:

    • PARP inhibitor

    • PARP inhibitor + Platinum based chemo

Local/Regional Recurrence:

• Consider initial treatment that patient received

• Surgical approach:

  • If previous lumpectomy + RT: consider mastectomy

  • If previous mastectomy: consider re-excision

• If stage III disease (LN+): consider neoadjuvant chemo

• CALOR Trial:

  • If HR-: Surgery → Adjuvant chemo

  • If HR+: Surgery → Adjuvant ET

Cancer in pregnancy

• Newly diagnosed breast cancer in the 1st trimester:

  • Mastectomy + axillary staging + can begin adjuvant chemotherapy in the 2nd trimester (if chemo is warranted)

• Radiation and anti-estrogen therapy should begin in the postpartum setting.

• Chemo is contraindicated in the first trimester, can be safely administered starting in the second trimester.

• Breast conserving surgery, requiring adjuvant RT is not recommended

• HER2 directed therapy and anti-estrogen therapy are contraindicated in pregnancy

Male Breast Cancer

• Associated with:

  • Family history of breast cancer

  • Black ethnicity

  • Exposure to RT to breast/chest

  • Genetic predisposition: BRCA1/BRCA2/CHEK2, PALB2

  • Exogenous estrogen use

  • Diseases associated with hyperestrogenism

• 90% of male breast cancers are invasive ductal carcinomas

• Treatment: Mastectomy + Tamoxifen

• If progression:

  • LHRH analog therapy + Aromatase inhibitor

  • LHRH analog therapy + Cyclin 4/6 inhibitor

Inflammatory Breast Cancer

• Treatment: Neoadjuvant chemo even if resectable upfront 

• Considered T4d lesion

Paget Disease of the breast

• Presents with crusting, itching of nipple with discharge

• Typically occurs in women >50 yo

• Important to undergo mammogram and breast US to rule out DCIS or IDC

• Treatment:

  • Endocrine

  • Chemotherapy

  • Radiation

  • Bone Health

  • Clinical Trial

Phyllodes Tumor

• Excisional biopsy → Wide excision

• Consider adjuvant RT if borderline or malignant phyllodes tumor completely excised

• No adjuvant chemo or ET in phyllodes tumor