Tx for DCIS,Radiation,Chemo

Question 1

DCIS calcifications

Answer 1

• tend to cluster closely together
  are pleomorphic, and may be linear or branching,
  suggesting their ductal origin.

Question 2

Findings on mammography in patients with DCIS

Answer 2

• clustered calcifications without an associated density
  in 75% of patients
• calcifications coexisting with an associated density
  in 15%
• density alone in 10%.

Question 3

Treatment recommendations for a patient with DCIS

Answer 3

based on
- the extent of disease within the breast
- histologic grade
- ER status
- presence of microinvasion
- patient age and preference

Question 4

Treatment options for DCIS include

Answer 4

mastectomy
breast-conserving surgery with irradiation
and breast-conserving surgery alone

breast conservation or unilateral mastectomy
there is also the option of adjuvant hormonal therapy
with tamoxifen to reduce the risk of local recurrence
or contralateral breast cancer.

Question 5

When to go for mastectomy for DCIS

Answer 5

1. Diffuse suspicious mammographic calcifications
   suggestive of extensive disease
2. Inability to obtain clear margins with breast-conserving
   surgery
3. Likelihood of a poor cosmetic result after breast-
   conserving surgery
4. Patient not motivated to comply with follow-up
   surveillance imaging
5. Patient choice
6. Contraindications to radiation therapy

Question 6

Use of Radiation and Hormonal Therapy

Answer 6

• adjuvant whole breast radiation therapy has
  been demonstrated in prospective randomized trials
  to decrease the risk for local recurrence.
• The use of hormonal therapy in patients with
  ER-positive DCIS can decrease further the risk
  for local recurrence and reduces the risk for
  development of new contralateral and ipsilateral
  breast cancers.

Question 7

When not to consider Radiation ?

Answer 7

• WBI after lumpectomy should be recommended
  for most patients with DCIS.
• The one subgroup that appears to have
  favorable outcomes without radiation are
  patients with small-tumor, low-grade or intermediate-grade lesions.

> > Patients with low-grade or intermediate-grade
DCIS measuring 2.5 cm or smaller had a 5-year rate
of ipsilateral breast recurrence of only 6.1%.

> > In contrast, patients with high-grade disease had
a much higher 5-year ipsilateral breast recurrence
rate of 15.3%.

Question 8

Patients at highest risk for local recurrence—and most likely to benefit from tamoxifen

Answer 8

positive margins
comedonecrosis
a mass on physical examination
and age younger than 50 years.

Question 9

SLNB in DCIS

Answer 9

• Sentinel node surgery is currently recommended
  in patients undergoing mastectomy for DCIS because
  20% to 30% of patients with DCIS on a diagnostic CNB
  are found to have invasive cancer on detailed
  evaluation of the mastectomy specimen
• For patients undergoing breast-conserving surgery
  for DCIS, sentinel node surgery may be considered
  for patients with larger areas of DCIS, particularly
  patients with high-grade histology or with
  high suspicion of microinvasion

Question 10

Which group avoid Radiation in Breast Cancer ?

Answer 10

The only group identified that might have been able
to avoid irradiation safely is patients older than
70 years who undergo lumpectomy and
adjuvant hormonal therapy for a stage I ER-positive
breast cancer.

Question 11

Patient who will not require Radiation

Answer 11

For patients with T1N0 or T2N0 breast cancer,
mastectomy and SLND provide effective local control
and radiation therapy is not required

Question 12

Which stage require radiation therapy

Answer 12

patients with stage III breast cancer have high rates
of locoregional recurrence after treatment
with a modified radical mastectomy and
adjuvant or neoadjuvant chemotherapy.

Question 13

Radiation therapy to which stage ?

Answer 13

There is consensus that patients with four
or more positive lymph nodes or
other features characteristic of stage III disease
should be counseled to undergo radiation therapy

Question 14

it is reasonable to consider postmastectomy radiation therapy only for selected patients with stage II disease, such as

Answer 14

• patients with extracapsular extension
• lymphovascular invasion
• age 40 years or younger
• close/positive surgical margins
• a nodal positivity ratio
  (ratio of positive nodes to total nodes examined)
  of 20% or greater
• patients who have undergone less than a
  standard level I or II axillary dissection

Question 15

American Society for Radiation Oncology guidelines for accelerated partial breast irradiation.

Answer 15

“Suitable” Group :
Age (years) : ≥60

Tumor size (cm) : ≤2
T stage : T1
Margins : Negative by at least 2 mm
Histology: Invasive ductal carcinoma
or other favorable subtypes
Pure DCIS: Not allowed
Grade: Any
LVI: None

ER status: Positive

Multicentricity: Unicentric

Multifocality: Clinically unifocal with total size ≤2 cm

N stage pN0

Treatment factors :
Neoadjuvant chemotherapy:
Not allowed

Question 16

21-gene recurrence score assay Oncotype DX

Answer 16

developed in an attempt to identify a specific
molecular phenotype of a tumor in an individual
patient and use the phenotype to predict the response
to therapy or provide information regarding prognosis.

This assay was validated first in patients with
ER-positive, lymph node–negative breast cancer

prognostic for OS and predictive of the benefits
of different systemic therapies, with higher
recurrence scores predicting increased benefit
from chemotherapy and lower scores predicting
lesser benefit from chemotherapy and increased
benefit from endocrine therapy

Question 17

TAILORx

Answer 17

• Patients with a recurrence scores less than 11 received endocrine therapy.
• Patients with a recurrence scores greater than 25 received chemotherapy.
• There were 6711 patients who had midrange recurrence
  scores of 11 to 25 and were randomly assigned to
  receive either chemoendocrine therapy or
  endocrine therapy alone.

Question 18

TAILORx results

Answer 18

chemotherapy is not recommended for patients
with hormonal receptor–positive, HER-2–negative
and node-negative disease and recurrence scores of
less than 25 for women over 50 years of age

or recurrence scores of less than 16.

Endocrine therapy was noninferior to chemoendocrine
therapy in the analysis of invasive DFS, invasive disease
recurrence, second primary cancer, and OS at 9-year
follow-up

Some benefit of chemotherapy was found in women 50
years of age or younger with a recurrence score of
16 to 25.

Question 19

Chemotherapy

Answer 19

• anthracyclines (e.g., doxorubicin, epirubicin)
• and taxanes (e.g., paclitaxel, docetaxel).
• The anthracyclines, which act as
  topoisomerase II inhibitors and antimetabolites
• anthracyclines are associated with a 16% reduction
  in the risk of death and an 11% reduction in the
  risk of recurrence
• Anthracyclines are associated with the potential
  long-term toxic effect of cardiomyopathy
• The risk of cardiac dysfunction resulting
  from anthracyclines is dose dependent
• An additional dangerous risk of anthracycline-based
  chemotherapy is the risk of development of
  leukemia (<1%).

Question 20

Taxanes (microtubule inhibitors)

Answer 20

active not only in tumors previously unexposed
to chemotherapy
but also in anthracycline-resistant tumors.

The taxanes are associated with the potential
permanent toxic effect of peripheral neuropathy

Question 21

EBCTCG analysis published in 2012

Answer 21

On average, the taxane-plus-anthracycline–based control
regimens were superior to standard AC but were not
superior to anthracycline regimens with extra cycles (i.e.,
CAF or CEF).

Cytoxin/Adriamycin/fluorouracil (CAF)
or Cytoxin/epirubicin/fluorouracil (CEF)

a chemotherapy regimen that include a taxane or
anthracycline regimens with higher cumulative dosages
reduced breast cancer mortality by approximately one
third.

Question 22

HER-2 gene

Answer 22

• amplification or protein overexpression occurs
  in approximately 20% to 25% of breast cancers.
• Amplification leads to protein overexpression
  measured clinically by immunohistochemistry and
  scored on a scale from 0 to 3+.
• Alternatively, fluorescence in situ hybridization
  directly detects the quantity of HER-2 gene copies
• the normal copy number is two

Question 23

Trastuzumab

Answer 23

• humanized monoclonal antibody developed to target
  the extracellular domain of the HER-2 receptor.
• When trastuzumab is used as a single agent for
  treatment of metastatic breast cancer, response is seen in
  approximately 30% of patients.

Trastuzumab combined with chemotherapy is even
more effective, with synergy seen with multiple agents.

Trastuzumab-based chemotherapy regimens improve DFS and OS for patients with metastatic disease.

Question 24

Duration

Answer 24

established 1 year of treatment as standard of care

Question 25

trastuzumab-based therapy

Answer 25

Patients receiving trastuzumab-based therapy in NSABP B-31 (AC followed by paclitaxel-trastuzumab) had an increased risk of cardiac dysfunction, with a 3-year event rate of 4.1% versus 0.8% in the control arm. Patients with lower ejection fraction at the initiation of therapy, older age, or hypertension were at highest risk of cardiac dysfunction

Question 26

AC followed by docetaxel-trastuzumab (AC-TH) and docetaxel combined with carboplatin and trastuzumab (TCH)

Answer 26

- Rates of cardiac toxic effects were markedly lower in the TCH group (0.37%) than in the AC-TH group (1.87%).

Question 27

Drugs Targeting HER2

Answer 27

- tyrosine kinase inhibitor lapatinib - the trastuzumab drug conjugate trastuzumab emtansine >> neratinib >> pertuzumab, a monoclonal antibody that inhibits dimerization of HER-2 with other HER-2 receptors. - The combination of trastuzumab and pertuzumab is approved in all disease settings - while trastuzumab/neratinib is approved in the adjuvant setting - trastuzumab/lapatinib in metastatic disease.

Question 28

Tamoxifen

Answer 28

- Tamoxifen is a selective ER modulator that has antagonistic and weak agonistic effects. - It is generally well tolerated - the most common side effect is hot flashes or vasomotor symptoms increased risk of thromboembolic disease and uterine cancer.

Question 29

Tamoxifen Benefit

Answer 29

- administered for 5 years was found to reduce the risk of recurrence of breast cancer for patients with hormone receptor–positive disease by 41% - beneficial for premenopausal and postmenopausal women - similar magnitude of benefit for patients with lymph node–positive and lymph node–negative disease. - The duration of therapy with tamoxifen was also evaluated - 5 years of therapy was found to be superior to only 1 to 2 years of therapy in terms of breast cancer recurrence

Question 30

Why and when 10 years ?

Answer 30

- Longer Against Shorter (ATLAS) trial showed an approximately 25% reduction in the rate of recurrence and approximately 3% reduction in mortality risk in women taking 10 years of tamoxifen versus 5 years, with the benefit being most pronounced after year 10. - . For premenopausal or perimenopausal women, tamoxifen for 5 years is recommended. After 5 years, if the patient is still premenopausal, she should be offered an additional 5 years of tamoxifen therapy

Question 31

Aromatase Inhibitors

Answer 31

- AIs block the conversion of the hormone androstenedione into estrone by inhibition of the aromatase enzyme.

Question 32

Why AI used for Postmenopausal

Answer 32

Selective AIs, which include anastrozole, exemestane, and letrozole, are unable to suppress ovarian function completely in a premenopausal or perimenopausal woman and are restricted for use in postmenopausal women

Question 33

In the most recent ASCO guidelines

Answer 33

if women are pre- or perimenopausal and have received 5 years of adjuvant tamoxifen, they should be offered 10-years total duration of tamoxifen. If women are postmenopausal and have received 5 years of adjuvant tamoxifen, they should be offered the choice of continuing tamoxifen or switching to an AI for 10-years total adjuvant endocrine therapy.

Question 34

Ovarian Ablation

Answer 34

the consensus guidelines state that if the patient has high-risk disease, then ovarian suppression should be considered in addition to hormonal suppression.

Question 35

Neoadjuvant therapy

Answer 35

the administration of systemic chemotherapy or endocrine therapy before surgery, can result in a significant reduction in tumor size and convert inoperable tumors to operable ones significant reduction in tumor size and convert inoperable tumors to operable ones

Question 36

Benefit of Neoadjuvant in terms of recurrence and BCS

Answer 36

- The breast conservation rate was higher in women completing neoadjuvant chemotherapy - the rate of in-breast recurrence in women who underwent neoadjuvant therapy followed by lumpectomy was not significantly different from the rate of in-breast recurrence in women who underwent lumpectomy before adjuvant chemotherapy.

Question 37

Delivering chemotherapy before surgery has other theoretical advantages

Answer 37

- potential to lower the volume of microscopic metastatic disease - decrease drug resistance by treating tumors before resistance has developed - increase the efficacy of treatment because the vascular system has not been disrupted by surgery - permit evaluation of the response to treatment in vivo

Question 38

what to do before neoadjuvant

Answer 38

Consequently, a metallic clip is placed at the primary tumor site under image guidance before neoadjuvant chemotherapy is initiated to allow identification of the original tumor site for excision after therapy.

Question 39

SLND before or after Neoadjuvant

Answer 39

some centers performing SLND before neoadjuvant therapy in patients with clinically negative nodes to inform decisions about systemic and radiation therapy SLND is feasible and accurate after neoadjuvant chemotherapy, resulting in sentinel node identification rates of approximately 91%.

Question 40

More

Answer 40

neoadjuvant chemotherapy eradicates microscopic disease in the regional nodes in 40% of patients, reducing the need for complete ALND at the time of surgical intervention. Complete ALND remains the standard for all patients receiving neoadjuvant therapy who have biopsy-proven, node-positive disease at initial presentation; however, there is significant interest in identifying patients in whom SLND might be appropriate after neoadjuvant chemotherapy.

Question 41

Decrease False negative SLNb after Neoadjuvant

Answer 41

The false-negative rate was lower when dual tracers were used for mapping (false-negative rate, 10.8%) and when three or more sentinel nodes were identified (false- negative rate, 9.1%)

Question 42

Target Axillary Dissection

Answer 42

surgical technique is critical in reducing the false-negative rate for SLND in patients with clinically node-positive disease receiving neoadjuvant chemotherapy. If a clip is left in the positive axillary node prior to chemotherapy and that clip and the SLN are retrieved at the time of axillary surgery (targeted axillary dissection), then the false-negative rate was lowered in a single institution trial to 1.4%.

Question 43

Targeted Therapy as neoadjuvant , HER2

Answer 43

- pathologic complete response, which was seen in 46% of patients in the pertuzumab and trastuzumab plus docetaxel - A pathologic complete response was shown in 17% of patients in the trastuzumab plus pertuzumab arm, suggesting that some patients with HER-2–positive breast cancer could be treated with targeted therapy alone without chemotherapy.

Question 44

Targeted therapy, ER

Answer 44

- patients with ER-positive disease can be treated with endocrine therapy as neoadjuvant therapy, - optimal in postmenopausal women with ER-positive tumors for whom endocrine therapy provides more protection than standard chemotherapy against risk of recurrence and death caused by breast cancer.