Breast cancer Flashcards
Epidemiology
Most common malignancy in women in the US
2nd most common cause of cancer related death in women
Men do get breast cancer
Risk factors
More than 60% of patients will not have any risk factors
Age
Family history–> number of 1st and 2nd degree relatives with disease increases risk
Personal hx
Prior radiation
Estrogen exposure–> endogenous
Exogenous estrogen–> OC/HRT
Risk factors continued
Alcohol
Prior breast biopsies with proliferative histology
Nulliparity or age > 30 years old before first birth
Obesity/Diet: estrogen stores in fat
Genetics
Only 5-10% of breast cancers are familial
Tumor supressor genes:
BRCA-1: increased risk of ovarian cancer
BRCA-2: great risk of breast cancer, lower risk of ovarian, greater in male breast cancer
History of disease
Malignant progression involves early changes in proliferation by systemic hormones
Sites of metastasis: Bone, liver, lungs, brain, distant lymph nodes and/or skin
Presentation
> 90% of patients present with a painless lump in the breast
< 10% of patients have stabbing or aching pain as the first symptom
Other presentations include: nipple discharge, retraction, or dimpling
In more advanced cases, prominent skin edema, redness, warmth, and induration of underlying tissue
Presentation continued
Asymptomatic disease may be detected on screening mammography
10% of patients will present with metastatic disease and for those patients, the symptoms mirror their metastatic site: bone pain, SOB
50% of patients with an initial diagnosis of breast cancer will ultimately develop metastatic disease despite potentially curative multimodality therapy
Diagnosis
History and PE, clinical breast exam, 3-D mammogram, and potentially a breast ultrasound
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Prognostic tools
Oncotype DX
Can determine the likelihood of the breast cancer returning and whether the patient will benefit from chemo or not
Oncotype DX
Low risk (<26)=hormonal therapy only
High risk (>26)=chemotherapy and hormonal therapy
Women < 50 yo and score of 16-25 did incur benefit from chemotherapy
Neoadjuvant and Adjuvant Therapy
Stage 1, IIA, IIB, III dx
Goal of therapy is to achieve cure
Neoadjuvant therapy
For patients with larger tumors (>1 cm)
- allows less extensive surgery
- allows you to see response to chemotherapy while the tumor is still in tact
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Adjuvant hormonal therapy
Surgical ablation–>Oophorectomy
SERMS–>Tamoxifen (pre/post menopausal)
LHRH agonists–>Leuprolide (premenopausal), Goserelin
Aromatase inhibitors–>postmenopausal
Premenopausal at diagnosis
T x 5 yrs +/- OS OR AI x 5 yrs + OS
Premenopausal
1. T x 5 more years to complete a total of 10 years or
- No further endocrine therapy
Postmenopausal
1. Could consider an additional 5 years of AI to total 10 years OR
- Consider T x 5 more yrs to complete 10 years
Postmenopausal at diagnosis
AI x 5 yrs then consider AI for additional 5 years
Chemotherapy regimens
Standard chemo consists of 4-6 cycles given every 3-4 weeks
Neoadjuvant consists of 4-6 cycles
Adjuvant Chemotherapy Regimen for HER2 negative
Dose Dense AC–> Paclitaxel
Doxorubicin
Cyclophosphamide
Repeat every 2 weeks x 4 (Must give growth factors) followed by: Paclitaxel every 2 weeks x 4 (must give growth factors) or weekly x 12 weeks
TC: Docetaxel and cyclophosphamide; repeat every 3 weeks x 4
Chemotherapy considerations
Discussion of whether to have an anthracycline based regimen or non-anthracycline based regimen
Cardiac risks
If cardiac problems, can consider docetaxel and cyclophosphamide regimen
Adjuvant HER2 Postive regimens
APT:
-Paclitaxel weekly x 12 weeks
-Trastuzumab with the first dose of paclitaxel
Followed by: Trastuzumab weekly x 11 weeks, every 3 weeks for 1 year
TCH:
-Docetexal, Carboplatin, Trastuzumab–>repeat every 3 weeks x 6
Followed by: Trastuzumab every 3 weeks weekly to complete 1 year of trastuzumab
TCH-P:
-Docetaxel, Carboplatin, Trastuzumab, Pertuzumab–> repeat every 3 weeks x 6
Followed by: both trastuzumab and pertuzumab to complete 1 year
Adjuvant Chemotherapy regimen for Triple negative dx
AC + Pembrolizumab–> 3 weeks x 4
Pembrolizumab-> repeat every 3 weeks x 4; followed by: AC
Pembrolizumab every 3 weeks for total of 1 year
Metastatic dx
Goal of therapy is palliative
Median survival is 3 years
Symptomatic dx: Chemo
ER/PR + tumors tend to be more indolent
HER2 Targeted Regimens (metastatic setting)
1st line option:
-Trastuzumab
-Pertuzumab
-Docetaxel
OR
-Trastuzumab
-Pertuzumab
-Paclitaxel
Given every 3 weeks
HER2-low patients
Fam-trastuzumab deruxtecan
Has shown benefit after failed treatment
TNBC (metastatic setting)
Platinum agents have shown benefit:
Carboplatin single agent (1st line)
Cisplatin single agent (1st line)
Pembrolizumab + chemo is better than chemo alone in patients with a combined positive score of > 10
Hormonal therapy (metastatic setting)
HER2 negative and Pre/post menopausal receiving OS
1st line: AI + CDK 4/6 inhibitor
2nd line: Fluvestrant + CDK inhibitor if not used before
OR
Everolimus + endocrine therapy
Abemaciclib
1st line + AI
2nd line + Fluvestrant
2nd line as a single agent
Monitoring parameters: Complete blood counts, diarrhea, elevation in LFTs, pneumonitis, and thromboembolism
Palbociclib
3 weeks then 7 days off
1st line + AI
2nd line + fluvestrant
Monitoring parameters: Complete blood count, diarrhea, elevation in LFTs, pneumonitis
Ribociclib
3 weeks then 7 days off
1st line + AI
2nd line + fluvestrant
Monitoring parameters: complete blood count, diarrhea, elevation in LFTs, QTc prolongation (ECG), pneumonitis
Mammogram
Age 40-44 opportunity for annual exams
Age 45-54: annual
Age > or equal to 55: Biennial mammograms or the opportunity for annual exams
Breast cancer prevention
Prophylactic mastectomy
Bilateral oophorectomy
Tamoxifen
Raloxifene
Exemestane
Hormone postive, HER2 negative, lymph-node negative (premenopaunsal)
Asses tumor:
Tumor < 0.5 cm–> adjuvant endocrine therapy
Pre-menopausal:
Regimen: GnRH agonist + AI x 5 years
- If still premenopausal–>Tamoxifen x 5 years or no further endocrine therapy
-If postmenopausal after–> AI x 5 years or Tamoxifen x 5 years
Agents:
Oophorectomy
SERM
GnRH agonists (monthly or q3 months)
May add AI after OS via GnRH agonist
Hormone postive, HER2 negative, lymph-node negative (postmenopausal)
Aromatase inhibitor x 5 years and consider for 5 more
Agents:
SERM
AI
