Breast Locally Advance

Question 1

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

Answer 1

Inflammatory breast cancer

Question 2

Hallmarks of inflammatory breast cancer:

Answer 2

Hallmarks
rapid disease onset
clinical findings: skin erythema, edema (peau d’orange), brawny breast induration, warmth, and asymmetric enlargement

Question 3

Most common presentation of locally advanced breast cancer

Answer 3

Palpable mass

Question 4

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

Answer 4

35%

Question 5

preferred imaging technique if leptomeningeal carcinomatosis is suspected

Answer 5

Gadolinium-enhanced MRI (Brain)

Question 6

In inflammatory breast cancer:
What are the substances/genes or factors that are

Elevated?

Decreased/Loss?

Answer 6

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

Question 7

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?

Answer 7

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)

Question 8

NSABP-B18 and EORTC
Compared neoadjuvant vs adjuvant chemotherapy for patients with stage II or stage III breast cancer

What is the conclusion?

Answer 8

Conclusion

Neoadjuvant chemotherapy offered an advantage because of higher breast conservation rates

Question 9

In MD Anderson series
BCT after neoadjuvant chemotherapy

Factors independently associated with breast cancer recurrence and local-regional recurrence?

Answer 9

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

Question 10

Standard of care for patients with clinically positive lymph nodes or locally advanced disease

Answer 10

MRM

Question 11

Early Breast Cancer Trialists’ Collaborative Group

What Lymph node status grouping has statistically significant improvement in death and overall survival in post mastectomy patients?

Answer 11

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%

Question 12

What is the optimal dose and treatment field in Post mastectomy RT?

Answer 12

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

Question 13

Based on the Danish 82b, 82c and Vancouver trial of Postmastectomy RT patients.

What is the overall conclusion?

Answer 13

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.

Question 14

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?

Answer 14

Most favorable prognostic features:

Question 15

Postmastectomy radiation therapy is reasonable:

Answer 15

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

Question 16

Three of the most important recent trials that have shown a benefit for adjuvant taxanes after anthracycline chemotherapy:

Answer 16

CALGB 9344/Intergroup 0148 trial
NSABP B-28 trial
BCIRG 001 trial

Question 17

Preferred hormonal treatment for all premenopausal women

Have ovarian function after chemotherapy

Answer 17

Tamoxifen

Question 18

Hormonal therapy for post menopausal patient:

Answer 18

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

Question 19

Adjuvant treatment:

tumors that have gene amplification of the HER2/neu gene

Answer 19

Trastuzumab

Question 20

No increase in cardiac events or other serious sequelae in Concurrent use of trastuzumab and radiation

True or false

Answer 20

True

Question 21

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%

Answer 21

Supraclavicular Lymph node disease

Question 22

How many percent of inoperable inflammatory breast cancer will provide clinical response with neoadjuvant chemotherapy?

Answer 22

80%

Question 23

Pre- op RT dose for inflammatory breast cancer?

Dose for Definitive RT?

Answer 23

50-51 Gy

72 Gy

Question 24

Post mastectomy RT for Inflammatory breast cancer can produce ____ % locoregional recurrence rates?

Answer 24

80

Question 25

Rationale behind the accelerated hyperfractionated Rt in inflammatorybreast cancer

Answer 25

Rapid doubling time

Question 26

The total dose of accelerated hyperfrac RT for Inflammatory breast cancer?

Answer 26

66 Gy 51 Gy/1.5 Gy 2x a day Plus Chest wall boost of 15 Gy/1.5 Gy 2x a day

Question 27

Remains the standard salvage treatment for disease that recurs in the breast after breast-conserving treatment.

Answer 27

Mastectomy

Question 28

Which is better? Autologous tissue reconstruction Or Tissue expander and implant

Answer 28

Autologous tissue reconstruction

Question 29

According to MD anderson series, the predictors of outcome for locoregional recurrence after mastectomy are?

Answer 29

Initial nodal status* Time to recurrence Ability to use RT to treat the recurrence

Question 30

Based on the Danish 82b and 82c trials, the factors showing poor outcomes for locoregional recurrence after mastectomy are?

Answer 30

``` Large initial primary tumor High number of positive lymph nodes Extracapsular extension Recurrence in the infraclavicular or supraclavicular regions Disease-free interval of ```

Question 31

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

Answer 31

Male breast cancer

Question 32

Risk factors for Male breast cancer?

Answer 32

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"

Question 33

What are the target sites of Post mastectomy RT?

Answer 33

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

Question 34

Advantages of CT simulation

Answer 34

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

Question 35

What is the dosimetry and dosage for post mastectomy RT?

Answer 35

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 ```

Question 36

The rationale behind the breast board with 10-15 degree angle?

Answer 36

Placed on a 10- to 15-degree angle board to flatten the slope of the chest wall in the region of the sternum

Question 37

Advantages and Disadvantages of Implant Based Reconstruction?

Answer 37

"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)" ```

Question 38

Advantages of Autologous tissue reconstruction

Answer 38

"ADVANTAGES: Immediate or delayed Optimal cosmetic outcome for Immediate Reconstruction "

Question 39

Downsides of immediate reconstruction?

Answer 39

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.

Question 40

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.

Answer 40

1. Mammographic screening resulted in a larger proportion of patients being diagnosed with earlier disease stages. 2. Women’s health initiatives and public education efforts that prompted women to seek medical care at the first sign of a breast mass. 3. Medical community has become better educated about appropriate standards for evaluating a breast mass.