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BCOP - Breast > Early Stage Breast Cancer > Flashcards

Early Stage Breast Cancer Flashcards

1
Q

EARLY STAGE BREAST CANCER

POOR Prognostic factors other than staging

A
  • Primary resistance to systemic chemotherapy
  • Estrogen- and/or progesterone-negative receptor status
  • High levels of proliferative markers (e.g. Ki-67, mitotic index)
  • Lymphatic/vascular invasion
  • Aneuploid tumors
  • Diabetes
  • Obesity
  • HER2 amplification/overexpression (predicts response to HER2-directed therapy)
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2
Q

Treatment Decision Making for Early-Stage Breast Cancer

Oncotype DX®

A

= Commercially available gene expression assay – screens for expression of 21 genes (16 cancerrelated genes and 5 control genes), resulting in a recurrence score (RS) from 0 to 100.

The higher the score the greater the risk of recurrence and greater the benefit for chemotherapy

Preferred by NCCN® because it provides prognosis and predicts benefit of chemotherapy

Plan B trial suggests no clinical benefit with chemo for patients with high clinical risk and low RS

Oncotype DX® can predict the benefit of adjuvant chemotherapy in women with HR-positive, HER2-negative, LN-POSITIVE breast cancer.

NCCN® lists Oncotype DX® as an option for select patients with 1 – 3 ipsilateral axillary lymph nodes (pN1) to guide the addition of combination chemotherapy to standard hormone therapy.

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3
Q

Treatment Decision Making for Early-Stage Breast Cancer

Mammaprint®

A

FDA approved gene expression assay – screens for expression of 70 genes, resulting in either a good prognosis or a poor prognosis classification on basis of risk of distant recurrence at 5 and 10 years

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4
Q

Treatment Decision Making for Early-Stage Breast Cancer

PAM50 (Prosigna®)

A

Gene expression assay that screens for expression of 50 genes (+ 5 control genes).

Predicts distant relapse-free survival and likelihood of recurrence at 10 years in ER-positive postmenopausal patients with LN-negative or LN-positive breast cancer treated with endocrine therapy.

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5
Q

Treatment Decision Making for Early-Stage Breast Cancer

Breast Cancer Index (BCI)

A

Predictive of benefit of extended adjuvant endocrine therapy

  • BCI (H/I) in the high range (5.1 – 10) demonstrated significant improvements in DFS with extended adjuvant endocrine therapy
  • BCI low patients (range 0 – 5) did not benefit from extended adjuvant therapy
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6
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

DCIS

Local management

A

NO SURIVIVAL DIFFERENCES BETWEEN 3 APPROACHES

  • Breast conserving surgery (BCS) (aka lumpectomy) + radiation therapy OR
  • Total mastectomy ± reconstruction OR
  • BCS without radiation

-> After BCS, radiation reduces recurrence rates of DCIS by about 50%; half of recurrences are invasive and half are DCIS

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7
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

DCIS

Endocrine Tx

A

Following BCS +/- RT, consider endocrine therapy for 5 years to decrease risk of ipsilateral recurrence in patients with ER-positive DCIS

  • PREmenopausal patients - Tamoxifen
  • POST menopausal patients - Aromatase inhibitors or tamoxifen
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8
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

Stage IA, IB, IIA, IIB Invasive Breast Cancers (Early Stage)
or
T3 N1 M0

GOALS OF THERAPY: CURE

A

Summary - Most patients are eligible for primary surgery ± radiation therapy. However, some patients who otherwise are candidates for BCS except for the size of the tumor (in relationship to the size of the breast) may be better served with neoadjuvant/preoperative chemotherapy to attempt to shrink the tumor and possibly allow for BCS.

Neoadjuvant therapy is also preferred for patients with
HER2-positive disease and TNBC if T ≥ 1c or N ≥ 1 (see additional information in section “Primary
(preoperative, neoadjuvant) systemic chemotherapy

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9
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

Stage IA, IB, IIA, IIB Invasive Breast Cancers (Early Stage)
or
T3 N1 M0

Locoregional therapy (surgery ± radiation therapy)

A

Total mastectomy + surgical axillary staging (if w/ axillary lymph node dissection, then called
modified radical mastectomy) ± reconstruction

OR

BCS (segmental mastectomy, lumpectomy, etc.) + surgical axillary staging + XR

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10
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

Stage IA, IB, IIA, IIB Invasive Breast Cancers (Early Stage)
or
T3 N1 M0

BCS + XRT CONTRAINDICATIONS
ABSOLUTE

A
  • Radiation prohibited during pregnancy
  • Diffuse suspicious or malignant appearing macrocalcifications on mammogram
  • Widespread disease that cannot be incorporated by local excision through a single incision that achieves negative margins with a satisfactory cosmetic result
  • Diffusely positive pathologic margin
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11
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

Stage IA, IB, IIA, IIB Invasive Breast Cancers (Early Stage)
or
T3 N1 M0

BCS + XRT CONTRAINDICATIONS
RELATIVE

A
  • Prior radiation therapy to chest wall or breast
  • Active connective tissue disease involving the skin (especially scleroderma and lupus)
  • Positive pathologic margin
  • Women with known or suspected genetic predisposition to breast cancer (consider prophylactic bilateral mastectomy)
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12
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

Stage IA, IB, IIA, IIB Invasive Breast Cancers (Early Stage)
or
T3 N1 M0

Surgical Axillary Staging

A
  • Axillary lymph node dissection (ALND)
    Required if:
    • Clinical LN-positive at diagnosis OR
    • Sentinel LN-positive or not identified
  • Lymphatic mapping with sentinel lymph node biopsy (SLNB) preferred
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13
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

Stage IA, IB, IIA, IIB Invasive Breast Cancers (Early Stage)
or
T3 N1 M0

Radiation therapy after mastectomy

A

See recommendations for RT in figure “Locoregional treatment of early stage breast cancer”

NOT RECOMMENDED FOR:
- Negative axilliary lymph nodes
AND
- Tumors <= 5cm
AND
- Negative Margins

Common for radiation therapy to follow chemotherapy when both are indicated

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14
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

Stage IA, IB, IIA, IIB Invasive Breast Cancers (Early Stage)
or
T3 N1 M0

Systemic adjuvant therapy for early-stage breast cancer

Appropriate therapies

A

Goal of therapy is CURE

Appropriate therapies:
- Endocrine Therapy
- Chemotherapy
- HER2-directed therapies
- Bisphosphonates

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15
Q

Treatment of Early Stage and Locally Advanced Breast Cancer

Stage IA, IB, IIA, IIB Invasive Breast Cancers (Early Stage)
or
T3 N1 M0

Systemic adjuvant therapy for early-stage breast cancer

ASCO Guidelines for when to consider adjuvant chemotherapy

A
  • LN Positive (>= 1 with macrometastatic deposit > 2mm)
  • ER-negative tumors with T > 5 mm
  • HER2-positive tumors
  • High-risk LN negative tumors with T > 5mm and >= 1 other high-risk feature: grade 3, triple negative, LVI positive, Oncotype Dx RS associated with an estimated distant relapse rate of > 15% at 10 years, or Her2-positive
  • Adjuvant! Online 10-year risk of death from breast cancer > 10%
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16
Q
  • HORMONE RECEPTOR-POSITIVE
  • HER2-POSITIVE (PRE- OR POSTMENOPAUSAL)
  • T <0.5cm

pN0

Systemic Adjuvant TREATMENT

A

Consider adjuvant endocrine therapy
± adjuvant chemotherapy
+ trastuzumab (if chemo administered)

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17
Q
  • HORMONE RECEPTOR-POSITIVE
  • HER2-POSITIVE (PRE- OR POSTMENOPAUSAL)
  • T <0.5cm

pN1m

Systemic Adjuvant TREATMENT

A

± adjuvant chemotherapy
+ trastuzumab (if chemo administered)
+ adjuvant endocrine therapy

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18
Q
  • HORMONE RECEPTOR-POSITIVE
  • HER2-POSITIVE (PRE- OR POSTMENOPAUSAL)
  • T = 0.6 - 1cm

Systemic Adjuvant TREATMENT

A

± adjuvant chemotherapy
+ trastuzumab (if chemo administered)
+ adjuvant endocrine therapy

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19
Q
  • HORMONE RECEPTOR-POSITIVE
  • HER2-POSITIVE (PRE- OR POSTMENOPAUSAL)
  • T > 1cm

Systemic Adjuvant TREATMENT

A

+ adjuvant chemotherapy
+ trastuzumab
+ adjuvant endocrine therapy

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20
Q
  • HORMONE RECEPTOR POSTIVE
  • HER2-NEGATIVE
  • POSTMENOPAUSAL

T < 0.5cm and pN0

Systemic Adjuvant TREATMENT

A

± adjuvant endocrine therapy a

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21
Q
  • HORMONE RECEPTOR POSTIVE
  • HER2-NEGATIVE
  • POSTMENOPAUSAL

T > 0.5cm and pN1m

Systemic Adjuvant TREATMENT

A

Strongly consider 21-gene RT-PCR assay if candidate for
chemotherapy

ASSAY results:
- NOT DONE: ± adjuvant chemotherapy
+ adjuvant endocrine
- RS <26: ± adjuvant chemotherapy
- RS >26: + adjuvant chemotherapy
+ adjuvant endocrine therapy

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22
Q
  • HORMONE RECEPTOR POSTIVE
  • HER2-NEGATIVE
  • POSTMENOPAUSAL

pN2/pN3 (≥ 4 positive nodes)

Systemic Adjuvant TREATMENT

A

+ adjuvant chemotherapy
+ adjuvant endocrine therapy

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23
Q
  • HORMONE RECEPTOR NEGATIVE

T ≤ 0.5cm
pN0
HER2 NEGATIVE

Systemic Adjuvant TREATMENT

A

no adjuvant therapy

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24
Q
  • HORMONE RECEPTOR NEGATIVE

T ≤ 0.5cm
pN0
HER2 POSITIVE

Systemic Adjuvant TREATMENT

A

± adjuvant chemotherapy
+trastuzumab (if chemo administered)

Consider adjuvant chemo with weekly paclitaxel and trastuzumab particularly for ER-, HER2+, stage I cancer

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25
Q
  • HORMONE RECEPTOR NEGATIVE

T ≤ 0.5cm
pN1m
HER2 NEGATIVE

Systemic Adjuvant TREATMENT

A

± adjuvant chemotherapy

1 year of adjuvant olaparib is an option for select patients with germline BRCA1/2 mutation after completion
of adjuvant chemotherapy.

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26
Q
  • HORMONE RECEPTOR NEGATIVE

T ≤ 0.5cm
pN1m
HER2 POSITIVE

Systemic Adjuvant TREATMENT

A

± adjuvant chemotherapy
+trastuzumab (if chemo administered)

Consider adjuvant chemo with weekly paclitaxel and trastuzumab particularly for ER-, HER2+, stage I cancer

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27
Q
  • HORMONE RECEPTOR NEGATIVE

T = 0.6 - 1cm

HER2 NEGATIVE

Systemic Adjuvant TREATMENT

A

± adjuvant chemotherapy

1 year of adjuvant olaparib is an option for select patients with germline BRCA1/2 mutation after completion
of adjuvant chemotherapy.

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28
Q
  • HORMONE RECEPTOR NEGATIVE

T = 0.6 - 1cm

HER2 POSITIVE

Systemic Adjuvant TREATMENT

A

± adjuvant chemotherapy
+trastuzumab (if chemo administered)

Consider adjuvant chemo with weekly paclitaxel and trastuzumab particularly for ER-, HER2+, stage I cancer

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29
Q
  • HORMONE RECEPTOR NEGATIVE

T > 1cm

HER2 NEGATIVE

Systemic Adjuvant TREATMENT

A

+ adjuvant chemotherapy

1 year of adjuvant olaparib is an option for select patients with germline BRCA1/2 mutation after completion
of adjuvant chemotherapy.

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30
Q
  • HORMONE RECEPTOR NEGATIVE

T > 1cm

HER2 POSITIVE

Systemic Adjuvant TREATMENT

A

+ adjuvant chemotherapy
+ trastuzumab

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31
Q

NODE POSITIVE

Stage IIA, IIB
HR NEGATIVE
HER2 NEGATIVE

Systemic Adjuvant TREATMENT

A

+ adjuvant chemotherapy

  • 1 year of adjuvant olaparib is an option for select patients with germline BRCA1/2 mutation after completion of adjuvant chemotherapy
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32
Q

NODE POSITIVE

Stage IIA, IIB
HR NEGATIVE
HER2 POSITIVE

Systemic Adjuvant TREATMENT

A

+ adjuvant chemotherapy
+ trastuzumab
± pertuzumab (if trastuzumab administered)

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33
Q

NODE POSITIVE

Stage IIA, IIB
HR POSITIVE
HER2 NEGATIVE

Systemic Adjuvant TREATMENT

A

See previous algorithm

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34
Q

NODE POSITIVE

Stage IIA, IIB
HR POSITIVE
HER2 POSITIVE

Systemic Adjuvant TREATMENT

A

+ adjuvant chemotherapy
+ trastuzumab
± pertuzumab (if trastuzumab administered)
+ adjuvant endocrine therapy

  • Consider extended adjuvant neratinib following adjuvant trastuzumab-containing therapy in HR-positive,
    HER2-positive patients with perceived high risk of recurrence
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35
Q

Endocrine therapy

A

Data suggests that patients with greater percentage of ER/PR positivity will have a higher probability of positive outcomes with endocrine therapies (OS, DFS, etc.)

The NCCN® panel recommends considering endocrine therapy in patients whose breast tumors show at least 1% ER+ and/or PR+ cells and withholding endocrine therapy if less than 1% for both ER and PR.

The guidelines state that ER-low-positive cancers (1-10%) often behave similar to ER-negative cancers and this should be considered in decision-making for adjuvant therapy

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36
Q

Timing of adjuvant endocrine therapy

A

Endocrine therapy given concurrently during chemotherapy has been shown to
decrease DFS

Chemotherapy is typically given first and then endocrine therapy, sequentially.

Endocrine therapy may be given sequential or concurrent with radiation

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37
Q

Endocrine options for premenopausal women

A

ASCO and NCCN® recommendations for initial therapy:
- Tamoxifen for 5 years
- Consider combination of ovarian ablation or suppression (OAS) + tamoxifen x 5 years or OAS + AI x 5 years for
patients at higher risk of recurrence

After 5 years of tamoxifen alone:
- If patient remains premenopausal, consider an additional 5 years of tamoxifen (total of 10 years) or no further therapy. (CONFLICTING DATA > 5yrs)

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38
Q

Endocrine options for postmenopausal women

A

AI for 5-10 years
- ASCO: AI for 10 years for women node-positive BRCA
- NCCN: Optimal duration uncertain (7.5-10 yrs)

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39
Q

Endocrine options for males with breast cancer

A

Treat similarly to postmenopausal women except that if AIs are used, they must be combined with an agent to suppress testicular steroidogenesis (such as an LHRH
agonist)

Tamoxifen x 5-10 yrs preferred. May consider LHRH + AI

40
Q

Tamoxifen (pre- and postmenopausal women)

Drug Interactions

A

CYP2D6 inhibitors (see details in survivorship section)

41
Q

Tamoxifen (pre- and postmenopausal women)

SIDE EFFECTS

A
  • hot flashes
  • vaginal discharge or dryness
  • menstrual irregularities
  • sexual dysfunction
  • venous thromboembolism (VTE)
  • cataracts
  • endometrial cancer and uterine sarcoma (postmenopausal patients)
  • decline in bone mineral density in premenopausal
    patients (protective effect on bone mineral density in postmenopausal patients)
  • hyperlipidemia
42
Q

Aromatase Inhibitors (postmenopausal women)

Agents

A

NONSTEROIDAL:
- Anastrozole
- Letroxole

STEROIDAL:
- Exemestane

43
Q

Aromatase Inhibitors (postmenopausal women)

SIDE EFFECTS

A

Side effects:
- hot flashes
- arthralgias/myalgias
- mild headache
- diarrhea
- bone loss (osteoporosis, fractures)
- vaginal dryness
- cardiovascular events

44
Q

Aromatase Inhibitors (postmenopausal women)

MYALGIA/ARTHRALGIA

A
  • up to 50% ow women receiving AI
  • onset typical 6 weeks may worsen over 1 yr
  • often not responsive to NSAID/APAP
  • Duloxetine, acupuncture, and exercise are several treatment strategies that have shown a decrease in AI-associated arthalgias
  • 40% may tolerate different AI
45
Q

AROMASTASE INHIBITORS (Postmenopausal women)

First-line adjuvant therapy compared with tamoxifen

A

Anastrozole – approved for adjuvant therapy for early stage breast cancer (1 mg daily for 5 years); ATAC trial found anastrozole superior to tamoxifen in terms of
disease-free survival (DFS)

Letrozole – approved for adjuvant therapy for early stage breast cancer (2.5 mg daily for 5 years); superior to tamoxifen (BIG 1-98 trial found letrozole superior to
tamoxifen in terms of DFS

Exemestane – The TEAM trial evaluated exemestane x 5 years vs. sequential tamoxifen x 2.5-3 years followed by anastrozole to complete 5 years. DFS at 10 years was 67% in both arms

46
Q

AROMASTASE INHIBITORS (Postmenopausal women)

Sequential adjuvant therapy after 2-3 years of tamoxifen (switching strategy)

A

Anastrozole
– 1 mg daily to complete 5 years of adjuvant endocrine therapy; superior to tamoxifen alone for 5 years.
- At 36-month follow-up, 45 events vs. 17 events (p=0.0002). DFS and local recurrence-free survival also significantly longer in anastrozole group

Exemestane (IES trial)
– 25 mg daily to complete 5 years of adjuvant endocrine
therapy; superior to tamoxifen alone for 5 years.
- At 30.6 month follow-up, 449 first events vs. 266 events

47
Q

AROMASTASE INHIBITORS (Postmenopausal women)

Second adjuvant therapy after 5 years of tamoxifen (extended strategy)

A

Letrozole (MA-17 trial) – 2.5 mg daily for another 5 years superior to placebo; DFS (HR 0.52; 95% CI 0.45-0.61) and OS (HR 0.61; 95% CI 0.52-0.71) was superior with letrozole compared to placebo

Exemestane (NSABP B-33) – 25 mg daily for another 5 years vs. placebo; stopped when MA-17 results available; recent report of available data (about half of initial
accrual goal) indicate non-significant benefit in 4-year DFS (91% vs. 89%; RR = 0.68; p=0.07) with 30 months median follow-up.

48
Q

AROMASTASE INHIBITORS (Postmenopausal women)

Extending duration of AI

A

5 years vs. 10 years
- OS did not significantly differ between groups

7 years vs. 10 years
Conclusion: Extending hormone therapy by 5 years to total of 10 years provided no benefit over 2-year extension to total of 7 years

All three selective AIs (anastrozole, letrozole, exemestane) have similar antitumor efficacy and similar toxicity profiles

49
Q

AROMASTASE INHIBITORS (Postmenopausal women)

CDK4/6 inhibitor + endocrine therapy for adjuvant treatment

A

ASCO Guidelines recommend that 2 years of adjuvant abemaciclib + endocrine therapy may be offered to patients with HR-positive, HER2-negative, LN-positive early breast cancer with a high risk of recurrence and a Ki-67 score ≥ 20%. The panel also recommends this combination may be offered to the broader ITT population (based on high-risk criteria as defined by MonarchE).

NCCN Guidelines® state to consider 2 years of adjuvant abemaciclib for patients meeting high-risk criteria as defined by MonarchE.

MonarchE: High-risk defined as: ≥ 4 positive LN OR 1 – 3 positive LN and tumor ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%

50
Q

Systemic adjuvant therapy for early-stage breast cancer

Adjuvant Chemotherapy

A

The optimal regimen in any clinical situation has not been determined; no standard regimen; many acceptable, evidence-based regimens demonstrate improvement in reducing the risk of recurrent breast cancer

LN-negative vs. LN-positive: controversial whether to include a taxane in addition to an
anthracycline-based regimen in LN-negative disease

ASCO guidelines recommend
the use of an anthracycline and taxane regimen for patients with high-risk features
(including patients with LN-positive disease).

51
Q

Systemic adjuvant therapy for early-stage breast cancer

TAXANE Based Regimens

A

Consider use of taxane-based regimens, such as docetaxel and cyclophosphamide (TC), for patients with lower risk disease features or those who are not candidates for an
anthracycline

TC x 4 cycles offers improved DFS and OS compared with AC x 4 cycles.

Higher risk of infection with TC

HER2-negative: DFS improved with Tax+AC vs. TCx6

52
Q

Systemic adjuvant therapy for early-stage breast cancer

ANTHRACYCLINE Based Regimens

A

Use of anthracyclines reduced recurrence by 25% (absolute difference of 8%) and reduced overall mortality by 16% (absolute decrease 5%) compared to no chemotherapy

An optimal-dose anthracycline 3-drug regimen (cumulative doxorubicin ≥ 240 mg/m2 or epirubicin ≥600 mg/m2 but no higher than 720 mg/m2) should be considered for patients with high-risk disease who will not receive a taxane

Cumulative dose of doxorubicin in two-drug regimens should not exceed 240mg/m2

53
Q

Systemic adjuvant therapy for early-stage breast cancer

Taxane-containing regimens

A

Incorporation of TAXANE significantly reduces the risk of:
- distant recurrence
- any recurrence
- breast cancer mortality
- overall mortality

TC x 4 cycles provides improved DFS and OS compared to AC x 4 cycles

54
Q

Systemic adjuvant therapy for early-stage breast cancer

Dose-dense (DD) therapy (every 2 weeks)

A

LN-positive breast cancer patients in the CALGB 9741 study were randomized after surgery to sequential versus concurrent chemotherapy:
- AC -> Pac vs. A -> Pac ->
C) and standard dose (Q 3 week) versus dose dense (AC -> Pac)

  • Pts receiving q2wk chemo had significantly prolonged DFS vs q3wk
  • NCCN lists dose dense AC regimens followed by a taxane over conventional AC q3wks followed by a taxane

-Growth factor support is recommended for all cycles of dose-dense chemotherapy

55
Q

Systemic adjuvant therapy for early-stage breast cancer

Role of additional adjuvant chemotherapy for patients with residual disease following
neoadjuvant chemotherapy

CAPECITABINE

A

CREATE-X was a phase III open-label trial that randomized 910 patients with HER2-negative stage I – IIIB breast cancer with residual disease following neoadjuvant chemo and surgery to placebo or adjuvant capecitabine 1,250 mg/m2 BID on days 1 – 14 every 21 days x 6 or 8 cycles (protocol extended to 8
cycles after 1st 50 patients were enrolled).
- DFS/OS favorable to capecitabine group

  • For Triple Negative: DFS and OS favored capecitabine
56
Q

Triple Negative Breast CA

CAPECITABINE

A

NCCN® and ASCO guidelines recommend considering the use of 6-8 cycles of adjuvant capecitabine in patients with TNBC and pathologic invasive residual
disease following standard neoadjuvant treatment with taxane-, alkylator-, and
anthracycline-based chemotherapy

  • NCCN® guidelines recommend administering following completion of XRT
  • ASCO guidelines state that the capecitabine dose of 1,250 mg/m2 BID used in the CREATE-X study is associated with higher toxicity in patients ≥ 65 years old
57
Q

Role of additional adjuvant chemotherapy for patients with residual disease following
neoadjuvant chemotherapy

OLAPARIB

A

Consider OLAPARIB in pts who have germline BRCA1/2 mutation AND:
- TNBC if:
≥pT2 or ≥pN1 disease after adjuvant chemotherapy OR residual dx following neoadjuvant tx
- HR+, HER- if:
≥ 4 positive LN after adjuvant chemotherapy OR residual dx following neoadjuvant tx

58
Q

Role of additional adjuvant chemotherapy for patients with residual disease following
neoadjuvant chemotherapy

Adjuvant ado-trastuzumab emtansine

A

Adjuvant ado-trastuzumab emtansine x 14 cycles is recommended by NCCN® for
patients with HER2-positive breast cancer and residual disease following preoperative therapy based on the results of the KATHERINE trial (see additional information in the HER2-Directed Therapy section below).

May be administered concurrent with XRT.

59
Q

Role of additional adjuvant chemotherapy for patients with residual disease following
neoadjuvant chemotherapy

Adjuvant pembrolizumab

A

Adjuvant pembrolizumab for up to 9 cycles of the q21 day regimen (or 400 mg every 6 weeks x 5 cycles) if patient received pembrolizumab + chemotherapy in the neoadjuvant setting (see more information in section below: Choice of neoadjuvant Regimen)

60
Q

Selected Regimens for Neoadjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

Dose-dense AC

A

Doxorubicin 60 mg/m2 - d1 Q14 days x 4 cycles

Cyclophosphamide 600 mg/m2 - d1 Q14 days x 4 cylcles

61
Q

Selected Regimens for Neoadjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

EC

A

[EPIRUB 100] d1 Q21 days x 8 cycles

[CTX 830] d1 Q21 days x 8 cycles

62
Q

Selected Regimens for Neoadjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

AC ⇒ Paclitaxel

A
  • [Dox 60] d1 Q21 days x 4 cycles
  • [CTX 600] d1 Q21 days x 4 cycles
  • [PAC 80] over 1h QW Q7 days x 12 wks
63
Q

Selected Regimens for Neoadjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

AC ⇒ Docetaxel

A
  • [DOX 60] d1 Q21 days x 4 cycles
  • [CTX 600] d1 Q21 days x 4 cycles
  • [DOC 100] d1 Q21 days x 4 cycles
64
Q

Selected Regimens for Neoadjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

TAC

A
  • [Doc 75] d1 Q21d x 6 cycles
  • [Dox 50] d1 Q21d x 6 cycles
  • [CTX 500] d1 Q21d x 6 cycles
65
Q

Selected Regimens for Neoadjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

TC

A

NCCN Preferred Regimen:

  • [DOC 75] d1 Q21d x 4 cycles
  • [CTX 600] d1 Q21d x 4 cycles
66
Q

Selected Regimens for Neoadjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

Dose-Dense AC FOLLOWED by
- Dose-Dense Pac
OR
- Weekly Pac

A

NCCN preferred

  • [DOX 60] d1 q14d x 4 cycles
  • [CTX 600] d1 q14d x 4 cycles
  • [PAC 175] d1 q14d x 4 cycles
    OR
  • [PAC 80] d1 q7d x 12 weeks
67
Q

Selected Regimens for Neoadjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

Pembrolizumab + chemo

Preoperative:

A
  • Pembrolizumab 200mg d1 Q21d x 4 cycles
  • [Paclitaxel 80] d1, d8, d15 Q21d x 4 cycles
  • [Carbo AUC 5] d1 Q21d x 4 cycles
68
Q

Selected Regimens for NeoAdjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

Pembrolizumab + chemo

Postoperative:

A
  • Pembro 200mg d1 Q21d x 9 cycles
  • [DOX 60] d1 Q21d x 4 cycles
  • [CTX 600] d1 Q21 x 4 cycles
69
Q

Selected Regimens for NeoAdjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

CMF

A
  • [CTX 100 PO] d1-14 Q28d x 6 cycles
  • [MTX 40] d1, d8 Q28d x 6 cycles
  • [5-FU 600] d1, d8 Q28d x 6 cycles
70
Q

Selected Regimens for NeoAdjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

Weekly paclitaxel + carboplatin
(neoadjuvant only)

A
  • [Paclitaxel 80] d1, 8, 15 Q 21 days x 4 cycles
  • [Carbo 5 or 6] d1 Q21 days x 4 cycles
71
Q

Selected Regimens for NeoAdjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

Weekly paclitaxel + weekly carboplatin

A
  • [Paclitaxel 80] d1, 8, 15 Q 28 days x 6 cycles
  • [Carbo 1.5-2 ] d1, 8, 15 Q 28 days x 6 cycles
72
Q

Selected Regimens for NeoAdjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

Olaparib (adjuvant only)

A

Designated by NCCN® as a preferred regimen

  • Olaparib 300mg BID q28d x 1 year
73
Q

Selected Regimens for NeoAdjuvant/Adjuvant Therapy for HER2-negative Breast Cancer

Olaparib (adjuvant only)

A

ADJUVANT:
- [Capecitabine 1,000-1,250] PO BID D1 – 14 Q 21d X 6 – 8 cycles
* Recommended in adjuvant setting only. Considered a NCCN® preferred regimen for patients with TNBC and residual disease after preoperative therapy. Considered “useful in certain circumstances” as maintenance therapy for TNBC following adjuvant chemotherapy.

MAINTENANCE
- [Capecitabine 650] PO BID D 1 – 28 Q 28 days 1 year

74
Q

Adjuvant HER2-Directed Therapy

TREATMENT option if NO RESIDUAL DISEASE PRESENT
- After therapy or if not therapy is given

A

NCCN Guidelines® recommend to complete up to 1 year of HER2 targeted therapy with trastuzumab +/- pertuzumab

75
Q

Adjuvant HER2-Directed Therapy

TREATMENT option if RESIDUAL DISEASE PRESENT
- After therapy or if not therapy is given

A

NCCN® and ASCO guidelines recommend adotrastuzumab emtansine alone x 14 cycles. If ado-trastuzumab emtansine is discontinued for
toxicity, then it is recommended to administer trastuzumab +/- pertuzumab to complete 1
year of therapy

76
Q

Adjuvant HER2-Directed Therapy

TRASTUZUMAB

A
  • Recommended for all HER2-POS patients with tumors > 1 cm
  • NCCN® and ASCO: trastuzumab should be considered in
    HER2-positive patients with tumors < 1 cm due to poor recurrence-free survival in pt population
  • Preferentially administered concurrently (not sequentially) with a non-anthracycline chemotherapy regimen
    • d/t CARDIOTOXICITY RISKS
  • Typically given concurrent with taxane-portion of the regimen
  • Can be administered with any acceptable adjuvant chemo
77
Q

Adjuvant HER2-Directed Therapy

PERTUZUMAB

A

NCCN® and ASCO guidelines include a recommendation to consider the addition of pertuzumab to trastuzumab in the adjuvant setting to complete up to 1 year of HER2
targeted therapy for patients with LN-positive disease
- insignificant benefit in node negative

There was a greater incidence of ≥ grade 3 diarrhea in the pertuzumab group

78
Q

Adjuvant HER2-Directed Therapy

Ado-trastuzumab emtansine

A

KATHERINE trial: Patients received adjuvant adotrastuzumab emtansine 3.6 mg/kg every 21 days or trastuzumab for 14 cycles
- 3-year iDFS was significantly higher in the ado-trastuzumab
emtansine group compared to the trastuzumab group (88.3% vs. 77%)

ATEMPT trial: stage I HER2+ breast cancer 3:1 to adotrastuzumab emtansine 3.6 mg/kg IV every 3 weeks x 17 cycles or paclitaxel + trastuzumab (TH – paclitaxel weekly x 12 weeks + trastuzumab x 1 year)
- Less neuropathy, alopecia for pts receiving kadycla
- 3-year iDFS was 97.8% for ado-trastuzumab emtansine

Added to NCCN Guidelines® as an option in the adjuvant setting

79
Q

Adjuvant HER2-Directed Therapy

Neratinib

A

NCCN® recommends to consider the use of extended adjuvant neratinib following
adjuvant trastuzumab-containing therapy in HR-positive patients with a perceived high
risk of recurrence

ASCO recommends to consider use in patients with early-stage, HER2-positive, HR-positive, node-positive disease.

Patients who began neratinib within 1 year of trastuzumab completion, those with
LN-positive disease, and those with HR-positive disease appeared to derive the
greatest benefit

80
Q

Neratanib

SIDE EFFECTS

A

Diarrhea: prophylaxis with loperamide +/- colestipol or budesonide or neratinib dose
escalation strategies have been shown to reduce the rate, severity, and duration of
neratinib-associated grade ≥ 3 diarrhea

Two-week dose escalation is recommended to minimize diarrhea
* Week 1 (days 1 – 7) -> 120 mg daily
* Week 2 (days 8 – 14) -> 160 mg daily
* Week 3 and beyond -> 240 mg daily

If dose escalation is not utilized, antidiarrheal prophylaxis is recommended with 1st 2 cycles (56 days) of treatment and should be initiated with the 1st dose of neratinib. Recommended loperamide prophylaxis:
* Weeks 1 – 2 -> 4 mg TID
* Weeks 3 – 8 -> 4 mg BID
* Weeks 9 – 52 -> 4 mg as needed (not to exceed 16 mg/day)

81
Q

Adjuvant bone-modifying agents (BMAs)

GUIDELINES

A

NCCN Guidelines® recommend to consider adjuvant bisphosphonate therapy for risk
reduction of distant metastasis for 3 – 5 years in postmenopausal patients (natural or
induced) with high-risk node-negative or node-positive disease

Adjuvant BMAs are not recommended for men with early-stage breast cancer to prevent
recurrence but may be used to prevent or treat osteoporosis.

82
Q

Adjuvant bone-modifying agents (BMAs)

DENOSUMAB

A

Current guidelines state that data are insufficient to make a recommendation on the use of denosumab in the adjuvant setting except to reduce risk of fractures in
postmenopausal (natural or induced) patients receiving adjuvant endocrine therapy

  • Denosumab significantly delayed time to first clinical fracture
83
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Operable stage IIIA (T3, N1, M0)

GUIDELINES

A

1) See guidelines for early stage breast cancer (listed above).

2) Local therapy or neoadjuvant systemic therapy followed by local therapy based on patient and disease factors (see below)

84
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

All other stage IIIA, IIIB, IIIC (non-inflammatory)

GUIDELINES

A
  • Primary (preoperative, neoadjuvant) systemic chemotherapy; HER2-directed therapy should be incorporated if HER2-positive.
  • If a response is demonstrated and tumor is operable, then local therapy would be
    performed.
  • Mastectomy or BCS +/- RT may be considered, depending on clinical situation.
85
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Preoperative (neoadjuvant) systemic chemotherapy

Benefits of neoadjuvant therapy:

A

1) Decrease the size of the tumor to minimize surgery

2) Determine response to chemotherapy (an important prognostic indicator especially for
triple-negative disease and HER2+ disease)

3) Allows modification or addition of adjuvant regimens among patients with HER2-positive
and TNBC with residual disease

4) Allows time for genetic testing

5) Allows time to plan breast reconstruction in patients electing mastectomy

86
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Neoadjuvant (primary, preoperative) vs. adjuvant systemic therapy

A

Meta-analysis of neoadjuvant vs. adjuvant systemic treatment

  • No significant difference in death, disease progression, or distant recurrence
87
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

NCCN Guidelines® - candidates for neoadjuvant therapy

A

1) Preferred for patients with inoperable breast cancer (inflammatory breast cancer, bulky or matted cN2 axillary nodes, cN3 nodal disease, cT4 tumors)

2) Patients with operable breast cancer, neoadjuvant therapy is preferred for those with:
- HER2-positive disease or TNBC, if cT ≥2 or cN ≥ 1
- Consider neoadjuvant therapy for cT1,N0
- Large primary tumor relative to breast size in a patient that desires breast conservation
- With clinically node-positive disease likely to become node-negative with preoperative
systemic therapy

3) Patients in whom definitive surgery may be delayed

88
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Choice of neoadjuvant regimen

A

NCCN Guidelines® recommend that in general, those chemotherapy regimens recommended in the adjuvant setting may also be considered in the preoperative setting

Preferred to complete standard regimen prior to surgery

89
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Choice of neoadjuvant regimen

  • TNBC
A

ASCO guidelines state that patients with TNBC should be offered an anthracycline and taxane-containing regimen.
- Carboplatin may be offered to patients with TNBC to increase pathologic CR (pCR) especially in patients at high clinical risk (such as node-positive disease)
- Consider a taxane-based regimen, such as docetaxel and cyclophosphamide, for lower-risk patients or those with cardiac risk factors

-Pembrolizumab + chemotherapy can be considered

90
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Choice of neoadjuvant regimen

  • Regimens for HER2-positive disease

TRASTUZUMAB

A

In general, those chemotherapy regimens recommended in the adjuvant setting may also be considered in the neoadjuvant setting and vice versa

  • Patients with HER2-positive disease should receive preoperative systemic therapy incorporating TRASTUZUMAB
  • Patients with node-positive or high-risk node-negative disease should be offered neoadjuvant therapy with an anthracycline and taxane or non-anthracycline-based regimen in combination with trastuzumab +/- pertuzumab
91
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Choice of neoadjuvant regimen

  • Regimens for HER2-positive disease

PERTUZUMAB

A

Pertuzumab received accelerated approval from the FDA in combination with docetaxel and trastuzumab for patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (ESBC)

  • Addition of pertuzumab to trastuzumab and docetaxel resulted in significant improvement in pCR
92
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Choice of neoadjuvant regimen

  • Postoperative Endocrine Therapy
A

Historically utilized for locally advanced breast tumors in elderly patients with poor PFS or limitations to chemo

  • NCCN® includes option of endocrine therapy alone for patients with ER-positive disease based on comorbidities or low-risk luminal biology based on clinical characteristics and/or genomic signatures.
  • ASCO recommends that postmenopausal patients with HR-positive, HER2-negative disease
    can be offered hormone therapy with an aromatase inhibitor to downstage disease

PREMENOPAUSAL: Should NOT routinely be offered neoadjuvant endocrine therapy

POSTMENOPAUSAL: AI preferred over tamoxifen

Optimal duration of neoadjuvant endcocrine tx not known (3-6mo)

93
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Choice of neoadjuvant regimen

  • Local therapy following primary/postoperative systemic therapy
A
  • Total Mastectomy + surgical axillary staging ± reconstruction
    OR
  • BCS + surgical axillary staging

All patients should receive chest XRT
Pts w/ lymph nodes should receive XRT to nodes

94
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Choice of neoadjuvant regimen

  • Nonresponders to primary/preoperative systemic therapy or less than operable tumors
A
  • Change to non-cross-resistant chemotherapy
    OR
  • Radiation to breast and supraclavicular area

If no response to non-cross resistant chemotherapy, then go to radiation

Residual disease following preoperative chemotherapy (see section above “Role of
additional adjuvant chemotherapy for patients with residual disease following neoadjuvant
chemotherapy “)

95
Q

Stage IIIA, IIIB & IIIC Invasive Breast Cancers (locally advanced, non-inflammatory)

Choice of neoadjuvant regimen

  • Inflammatory Breast Cancer (IBC) (Any T4d)
A
  • Distinct clinical entity; rare; poor prognosis; aggressive
  • often ER-neg; HER2-pos
  • no standard of care
  • treat as locally advanced dx
  • chemo similar to pts w/ locally advanced dx and trastuzumab + pertuzumab should be considered in HER2-pos

BCOP - Breast (6 decks)

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