Breast Locally Advance Flashcards
Subcategory of locally advanced breast cancer
Rare: only 2% of all breast cancers in the United States
Younger population
Lymph node involvement at the time of diagnosis is much more common than in those with noninflammatory breast cancer
More common distant metastases at diagnosis
Inflammatory breast cancer
Hallmarks of inflammatory breast cancer:
Hallmarks
rapid disease onset
clinical findings: skin erythema, edema (peau d’orange), brawny breast induration, warmth, and asymmetric enlargement
Most common presentation of locally advanced breast cancer
Palpable mass
Bone scans
Recommended for all patients with locally advanced disease
up to ____% of patients with clinical stage III cancer can show abnormal bone scan results
35%
preferred imaging technique if leptomeningeal carcinomatosis is suspected
Gadolinium-enhanced MRI (Brain)
In inflammatory breast cancer:
What are the substances/genes or factors that are
Elevated?
Decreased/Loss?
Inflammatory Breast CA
high histologic grade
high percentages of cells in S phase and aneuploidy
does not express the ER
expresses high levels of p53 and epidermal growth factor
HER2/neu overexpression less common
Propensity to overexpress RhoC GTPase
Decreased expression of the tumor suppressor gene WIPS3.26,27
Loss of MUC-1 (associated with poorer survival)
Over expression of E-cadherin
If the patient has a clinically inoperable locally advanced tumor like if an initial surgical procedure is not likely to completely resect all gross disease with achievement of negative surgical margins (most T4 and Inflammatory breast CA).
What is the initial management?
Neoadjuvant chemotherapy as the initial therapy
Approximately 80% to 90% show partial or complete clinical response
Preferred if an initial surgical procedure is not likely to completely resect all gross disease with achievement of negative surgical margins (most T4 and Inflammatory breast CA)
NSABP-B18 and EORTC
Compared neoadjuvant vs adjuvant chemotherapy for patients with stage II or stage III breast cancer
What is the conclusion?
Conclusion
Neoadjuvant chemotherapy offered an advantage because of higher breast conservation rates
In MD Anderson series
BCT after neoadjuvant chemotherapy
Factors independently associated with breast cancer recurrence and local-regional recurrence?
Factors independently associated with breast cancer recurrence and local-regional recurrence: clinical N2 or N3 disease lymphovascular space invasion a multifocal pattern of residual disease residual disease >2 cm in diameter
Standard of care for patients with clinically positive lymph nodes or locally advanced disease
MRM
Early Breast Cancer Trialists’ Collaborative Group
What Lymph node status grouping has statistically significant improvement in death and overall survival in post mastectomy patients?
In patients with one to three positive lymph nodes
24.7% -> 5.3%
In patients with four or more positive lymph nodes
40.6% -> 12.9%
What is the optimal dose and treatment field in Post mastectomy RT?
optimal dose as a between 40 and 60 Gy delivered in 2-Gy fractions
optimal treatment field arrangements: include both the chest wall and the regional lymphatics
reanalyzed the data from the Early Breast Cancer Trialists’ Collaborative Group according to the quality of radiation treatments
Based on the Danish 82b, 82c and Vancouver trial of Postmastectomy RT patients.
What is the overall conclusion?
Patients treated with radiation: lower long-term risk of isolated local-regional recurrence than did patients randomized to no radiation therapy.
Reducing local-regional recurrence, postmastectomy radiation therapy could improve overall survival.
Based on the Danish randomized trials, Greatest proportional survival advantage associated with postmastectomy radiation was found in the subgroups of patients with the most favorable prognostic features. What are the most favorable prognostic features?
Most favorable prognostic features:
Postmastectomy radiation therapy is reasonable:
Clinical T3 or T4 tumors or clinical stage III disease:
regardless of their response to the chemotherapy regimen
Clinical stage I or II breast cancer:
Four or more positive lymph nodes after chemotherapy
Unusual patient in whom the disease progresses
Primary tumor exceeds 5 cm in diameter
Three of the most important recent trials that have shown a benefit for adjuvant taxanes after anthracycline chemotherapy:
CALGB 9344/Intergroup 0148 trial
NSABP B-28 trial
BCIRG 001 trial
Preferred hormonal treatment for all premenopausal women
Have ovarian function after chemotherapy
Tamoxifen
Hormonal therapy for post menopausal patient:
Aromatase Inhibitors
Anastrozole for 5 years
Letrozole for 5 years
Initial tamoxifen for 2 to 3 years followed by exemestane
Tamoxifen for 5 years followed by 5 years of letrozole
Adjuvant treatment:
tumors that have gene amplification of the HER2/neu gene
Trastuzumab
No increase in cardiac events or other serious sequelae in Concurrent use of trastuzumab and radiation
True or false
True
poorer outcome treated with chemotherapy: 10-year survival rates of 25% AJCC recategorize as Stage IIIC from IV Chemo + Surg + RT: 5-year LRC rate: 77% 5-year OS rate: 47%
Supraclavicular Lymph node disease
How many percent of inoperable inflammatory breast cancer will provide clinical response with neoadjuvant chemotherapy?
80%
Pre- op RT dose for inflammatory breast cancer?
Dose for Definitive RT?
50-51 Gy
72 Gy
Post mastectomy RT for Inflammatory breast cancer can produce ____ % locoregional recurrence rates?
80
Rationale behind the accelerated hyperfractionated Rt in inflammatorybreast cancer
Rapid doubling time
The total dose of accelerated hyperfrac RT for Inflammatory breast cancer?
66 Gy
51 Gy/1.5 Gy 2x a day
Plus
Chest wall boost of 15 Gy/1.5 Gy 2x a day
Remains the standard salvage treatment for disease that recurs in the breast after breast-conserving treatment.
Mastectomy
Which is better?
Autologous tissue reconstruction
Or
Tissue expander and implant
Autologous tissue reconstruction
According to MD anderson series, the predictors of outcome for locoregional recurrence after mastectomy are?
Initial nodal status*
Time to recurrence
Ability to use RT to treat the recurrence
Based on the Danish 82b and 82c trials, the factors showing poor outcomes for locoregional recurrence after mastectomy are?
Large initial primary tumor High number of positive lymph nodes Extracapsular extension Recurrence in the infraclavicular or supraclavicular regions Disease-free interval of
Unusual: only 0.9% of the total new breast cancer cases
Death ratio: 21:17 (M:F)
Similar histopathologic spectrum
Except Lobular Invasive Carcinoma
More frequently:
ER-positive (estimated rate of 90%)
Tamoxifen: reduce recurrence and death
HER2/ neu–negative
Presenting symptom: breast mass or axillary adenopathy
MOSTLY: Locally advanced disease
Similar: Diagnostic work-ups and Treatment Decisions with the female
More advanced clinical stage disease: worse outcome
Mastectomy w/ or w/o postmastectomy radiation: most common local-regional treatment approach
Systemic treatments: clinically relevant risk of DM
Male breast cancer
Risk factors for Male breast cancer?
Conditions that affect testosterone and estrogen levels
History of an undescended testicle
History of orchiectomy
Klinefelter’s syndrome
“Family history of female breast cancer :
Germline mutations in the BRCA2 gene: 4-16%
More common in males than BRCA 1”
What are the target sites of Post mastectomy RT?
Chest wall - most common site of recurrent disease (2/3 – 3/4)
Draining Lymphatics:
Axillary nodes- Stage III disease (T3 N1, T4, or pathologic N2-3 disease)
- clinically relevant risk of recurrence axillary apex/supraclav
Supraclavicular nodes
10-year risk of recurrence in the axillary apex: 14% to 19%:
4 or more positive lymph nodes
20% or greater (+) lymph nodes
Extracapsular extension of disease (>2 mm)”
NOT included:
IMN - Controversial; Still ongoing Phase III Clinical trials
Advantages of CT simulation
Very useful to precisely delineate target volumes
Contouring the region helps to ensure that these targets fall within the desired isodose lines
Contouring the low axilla region also helps to more precisely conform the dose distribution to the area in need of treatment
What is the dosimetry and dosage for post mastectomy RT?
Initial fields and target volumes should be treated to a total dose of 50 Gy in 25 fractions over 5 weeks
A 3- to 5-mm bolus is used over the chest wall every other day or every day for 2 weeks (20 Gy total dose)
Radiation Boost
Chest wall: 10 Gy in 5 fractions
Unresected but initially involved adenopathy:
IMN, ICF, SCF
UTZ: Resolution ≤1 cm: 10 Gy
Persistent >1 cm: 16 GY
The rationale behind the breast board with 10-15 degree angle?
Placed on a 10- to 15-degree angle board to flatten the slope of the chest wall in the region of the sternum
Advantages and Disadvantages of Implant Based Reconstruction?
“ADVANTAGES:
Simpler surgical procedures
Avoid the donor-site morbidities of autologous tissue transfers
Women who do not have adequate volume of autologous tissue in donor sites”
"DISADVANTAGE: Immediate reconstruction procedure normal tissues are less compliant rib fractures and other injuries High rates of late contraction, fibrosis, implant fixation, and poor aesthetic outcome (6 months)"
Advantages of Autologous tissue reconstruction
“ADVANTAGES:
Immediate or delayed
Optimal cosmetic outcome for Immediate Reconstruction
“
Downsides of immediate reconstruction?
Radiation has adverse effects on the long-term aesthetics of breast reconstructions (implant-based reconstruction)
Reconstruction has a negative effect on the design and delivery of radiation treatment fields.
Decline in the percentage of cases of locally advanced disease at diagnosis:
Mammographic screening resulted in a larger proportion of patients being diagnosed with earlier disease stages.
Women’s health initiatives and public education efforts that prompted women to seek medical care at the first sign of a breast mass.
Medical community has become better educated about appropriate standards for evaluating a breast mass.
- Mammographic screening resulted in a larger proportion of patients being diagnosed with earlier disease stages.
- Women’s health initiatives and public education efforts that prompted women to seek medical care at the first sign of a breast mass.
- Medical community has become better educated about appropriate standards for evaluating a breast mass.
