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NCCN Guidelines® Insights
Breast Cancer, Version 1.2017
Featured Updates to the NCCN Guidelines
William J. Gradishar, MD1,*; Benjamin O. Anderson, MD2; Ron Balassanian, MD3; Sarah L. Blair, MD4; Harold J. Burstein, MD, PhD5;
Amy Cyr, MD6,*; Anthony D. Elias, MD7; William B. Farrar, MD8; Andres Forero, MD9; Sharon Hermes Giordano, MD, MPH10;
Matthew P. Goetz, MD11; Lori J. Goldstein, MD12; Steven J. Isakoff, MD, PhD13; Janice Lyons, MD14; P. Kelly Marcom, MD15;
Ingrid A. Mayer, MD16; Beryl McCormick, MD17; Meena S. Moran, MD18; Ruth M. O’Regan, MD18; Sameer A. Patel, MD12;
Lori J. Pierce, MD20; Elizabeth C. Reed, MD21; Kilian E. Salerno, MD22,*; Lee S. Schwartzberg, MD23; Amy Sitapati, MD4;
Karen Lisa Smith, MD, MPH24; Mary Lou Smith, JD, MBA25; Hatem Soliman, MD26; George Somlo, MD27; Melinda Telli, MD28;
John H. Ward, MD29; Dorothy A. Shead, MS30,*; and Rashmi Kumar, PhD30,*
Abstract
These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and
systemic therapy recommendations for hormone receptor–positive disease in the 1.2017 version of the NCCN Guidelines for Breast
Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available
at press time, can be found in the most recent version of these guidelines at NCCN.org.
J Natl Compr Canc Netw 2017;15(4):433–451
©
© JNCCN—Journal
JNCCN—Journal of
of the
the National
National Comprehensive
Comprehensive Cancer
Cancer Network
Network |
| Volume
Volume 15
15 Number 4 |
Number 4 | April
April 2017
2017
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Accreditation Statement All clinicians completing this activity will be issued a certificate
Physicians: National Comprehensive Cancer Network is accredited of participation. To participate in this journal CE activity: 1) re-
by the Accreditation Council for Continuing Medical Education view the educational content; 2) take the posttest with a 66%
(ACCME) to provide continuing medical education for physicians. minimum passing score and complete the evaluation at http://
NCCN designates this journal-based CE activity for a maximum education.nccn.org/node/80546; and 3) view/print certificate.
of 1.0 AMA PRA Category 1 Credit™. Physicians should claim
Release date: April 10, 2017; Expiration date: April 10, 2018
only the credit commensurate with the extent of their partici-
pation in the activity.
Nurses: National Comprehensive Cancer Network is accredited Learning Objectives:
as a provider of continuing nursing education by the American Upon completion of this activity, participants will be able to:
Nurses Credentialing Center`s Commission on Accreditation.
• Integrate into professional practice the updates to NCCN
NCCN designates this educational activity for a maximum of
1.0 contact hour. Guidelines for Breast Cancer
Pharmacists: National Comprehensive Cancer Network is • Describe the rationale behind the decision-making
accredited by the Accreditation Council for Pharmacy Edu- process for developing the NCCN Guidelines for Breast
cation as a provider of continuing pharmacy education. Cancer
JNCCN:
Kimberly Callan, MS, Senior Director, Professional and Patient Publications, NCCN, has disclosed that she has no relevant financial relationships.
Genevieve Emberger Hartzman, MA, Journal Production Specialist, NCCN, has disclosed that she has no relevant financial relationships.
CE Authors:
Deborah J. Moonan, RN, BSN, Director, Continuing Education, NCCN, has disclosed that she has no relevant financial relationships. (Employed by NCCN
until 2/17/17.)
Karen Kanefield, Manager, Continuing Education Accreditation and Program Operations, NCCN, has disclosed that she has no relevant financial relationships.
Kathy Smith, Manager, CE Grant Writing & Project Management, NCCN, has disclosed that she has no relevant financial relationships.
Kristina M. Gregory, RN, MSN, OCN, Vice President, Clinical Information Operations, NCCN, has disclosed that she has no relevant financial relationships.
Rashmi Kumar, PhD, Director, Clinical Information Operations, NCCN, has disclosed that she has no relevant financial relationships.
This activity is supported by educational grants from Astellas, AstraZeneca, Celldex Therapeutics, Clovis Oncology, Genomic Health, Inc., Kyowa Hakko
Kirin, Jazz Pharmaceuticals, Novartis Pharmaceuticals Corporation, and NOVOCURE. This activity is supported by an independent educational grant
from Merck Co., Inc.
©©JNCCN—Journal
JNCCN—Journalofofthe
theNational
NationalComprehensive
ComprehensiveCancer
CancerNetwork
Network | | Volume
Volume15 Number4 4 ||
15 Number April2017
April 2017
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LOCOREGIONAL TREATMENT OF CLINICAL STAGE I, IIA, OR IIB DISEASE OR T3, N1, M0k
Radiation therapy to whole breast with or without boost r to tumor bed
≥4 positiveq (category 1), infraclavicular region, supraclavicular area, internal mammary
axillary nodes nodes, and any part of the axillary bed at risk (category 1). It is common for
radiation therapy to follow chemotherapy when chemotherapy is indicated.
Version 1.2017 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any
form without the express written permission of NCCN®.
BINV-2
Overview
NCCN Categories of Evidence and Consensus Breast cancer is the most common malignancy in
women in the United States and is second only to
Category 1: Based upon high-level evidence, there lung cancer as a cause of cancer death. The American
is uniform NCCN consensus that the intervention Cancer Society estimates that 255,180 Americans
is appropriate. will be diagnosed with breast cancer and 41,070 will
Category 2A: Based upon lower-level evidence, there die of the disease in the United States in 2017.1 The
is uniform NCCN consensus that the intervention is therapeutic options for patients with noninvasive or
appropriate. invasive breast cancer are complex and varied. The
Category 2B: Based upon lower-level evidence, there NCCN Clinical Practice Guidelines in Oncology
is NCCN consensus that the intervention is appro- (NCCN Guidelines) for Breast Cancer include up-
priate. to-date guidelines for the clinical management of pa-
Category 3: Based upon any level of evidence, there tients with carcinoma in situ, invasive breast cancer,
is major NCCN disagreement that the intervention Paget’s disease, phyllodes tumor, inflammatory breast
is appropriate. cancer, and breast cancer during pregnancy. These
guidelines are developed by a multidisciplinary panel
All recommendations are category 2A unless otherwise
noted. of representatives from NCCN Member Institutions
with breast cancer–focused expertise in the fields of
Clinical trials: NCCN believes that the best management medical oncology, surgical oncology, radiation on-
for any cancer patient is in a clinical trial. Participation in
clinical trials is especially encouraged. cology, pathology, reconstructive surgery, and pa-
tient advocacy.
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LOCOREGIONAL TREATMENT OF CLINICAL STAGE I, IIA, OR IIB DISEASE OR T3, N1, M0k
kSeeNCCN Guidelines for Older Adult Oncology for special treatment qConsider imaging for systemic staging, including chest/abdominal ± pelvic diagnostic
considerations. CT with contrast, bone scan, and optional FDG PET/CT (See BINV-1).
lSee Surgical Axillary Staging (BINV-D). rSee Principles of Radiation Therapy (BINV-I).
mSee Axillary Lymph Node Staging (BINV-E) and Margin Status in Infiltrating uPostmastectomy radiation therapy may be considered for patients with multiple high-
Carcinoma (BINV-F). risk recurrence factors, including central/medial tumors or tumors >2 cm with other
pSee Principles of Breast Reconstruction Following Surgery (BINV-H). high-risk features such as young age and/or extensive LVI.
Version 1.2017 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any
form without the express written permission of NCCN®.
BINV-3
In the most recent version of NCCN Breast bidities,2–4 and therefore sentinel lymph node biopsy
Cancer Guidelines, Version 1.2017, the NCCN (SLNB) has replaced axillary evaluation for patients
panel included updated recommendations for situa- with clinically node-negative disease.
tions where axillary lymph node dissection (ALND) Based on several randomized trials, it is now ac-
can be omitted in women with stages I, II, and IIIA cepted that patients with a negative sentinel lymph
(T3N1M0) breast cancer; for whole-breast radia- node (SLN) do not need an ALND.5–8
tion therapy (WBRT) using hypofractionation, up- The ACOSOG Z0011 trial randomized women
dates regarding accelerated partial breast irradiation ≥18 years of age with T1/T2 tumors, <3 positive
(APBI) and regional nodal irradiation (RNI) in SLNs, undergoing lumpectomy and WBRT to ei-
women with early-stage breast cancer; and systemic ther SLNB alone (n=436) or ALND (n=420). In
therapy for women with hormone receptor–positive this study, no difference was seen in local recurrence,
breast cancer in the adjuvant and metastatic set- disease-free survival (DFS), or overall survival (OS)
tings. The full version of these guidelines is available between women with positive SLNs undergoing a
online (NCCN.org). completion ALND versus no ALND. Only estrogen
receptor (ER)–negative status, age <50 years, and
lack of adjuvant systemic therapy were associated
Surgical Axillary Staging for Stages with decreased OS.9 At a median follow-up of 6.3
I, IIA, IIB, and IIIA (T3N1M0) years, locoregional recurrences were noted in 4.1%
ALND is the standard of care for patients with of patients in the ALND group and 2.8% of those
clinically positive nodes. However, ALND is asso- in the SLNB group (P=.11). Median OS was ap-
ciated with lymphedema and other significant mor- proximately 92% in each group.10 Long term follow-
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aaThere are limited data to make chemotherapy recommendations for those >70 y of
bSee Principles of HER2 Testing (BINV-A).
age. See NCCN Clinical Practice Guidelines for Older Adult Oncology.
wMixed lobular and ductal carcinoma should be graded based on the ductal bbThe prognosis of patients with T1a and T1b tumors that are node negative is
component and treated based on this grading. For metaplastic carcinoma, the uncertain even when HER2 is amplified or overexpressed. This is a population of
prognostic value of the histologic grading is uncertain. However, when a specific breast cancer patients that was not studied in the available randomized trials. The
histologic subtype of metaplastic carcinoma is present and accounts for more than decision for use of trastuzumab therapy in this cohort of patients must balance the
10% of the tumor, the subtype is an independent prognostic variable. known toxicities of trastuzumab, such as cardiac toxicity, and the uncertain, absolute
xConsider adjuvant bisphosphonate therapy in postmenopausal (natural or induced)
benefits that may exist with trastuzumab therapy.
patients receiving adjuvant endocrine therapy. ccAdjuvant chemotherapy with weekly paclitaxel and trastuzumab (Tolaney et al.
yEvidence supports that the magnitude of benefit from surgical or radiation ovarian
NEJM 2015) can be considered for HER2-positive T1a N0 cancers, particularly if
ablation in premenopausal women with hormone receptor-positive breast cancer is the primary cancer is ER negative, and the tumor size borders on T1b (>5 mm).
similar to that achieved with CMF alone. See Adjuvant Endocrine Therapy (BINV-J). The absolute benefit of HER2-based systemic chemotherapy is likely negligible
zChemotherapy and endocrine therapy used as adjuvant therapy should be given
in patients with ER-positive cancers and tumor size bordering on T1mic (<1 mm),
sequentially with endocrine therapy following chemotherapy. Available data when the estimated recurrence risk is less than 5% and endocrine therapy remains
suggest that sequential or concurrent endocrine therapy with radiation therapy is a viable option for systemic treatment.
acceptable. See Adjuvant Endocrine Therapy (BINV-J) and Preoperative/Adjuvant ddA pertuzumab-containing regimen can be administered to patients with ≥T2 or ≥N1,
Therapy Regimens (BINV-K). HER2-positive, early-stage breast cancer.
Version 1.2017 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any
form without the express written permission of NCCN®.
BINV-5
up (median, 9.25 years) results of the ACOSOG the group treated with ALND versus those not treat-
Z0011 study showed no statistically significant dif- ed with ALND in 5-year DFS rate (84.4% [95% CI,
ference in local recurrence-free survival between 80.7%–88.1%] vs 87.8% [95% CI, 84.4%–91.2%]);
the groups (P=.13).11 The cumulative incidence of cumulative incidence of breast cancer events, includ-
ipsilateral axillary recurrences at 10 years was 0.5% ing local, regional, contralateral breast, and distant
(2 patients) in those who underwent ALND and recurrence (10.8% [95% CI, 7.6–14.0] vs 10.6% [95%
1.5% (5 patients) in those who underwent SLNB CI, 7.5–13.8]); or OS rate (97.6% [95% CI, 96.0%–
alone (P=.28).11 The 10-year cumulative incidence 99.2%] vs 97.5% [95% CI, 95.8%–99.1%]).12 Re-
of local regional recurrences was 6.2% with ALND gional recurrence was <1% for those who underwent
and 5.3% with SLNB alone (P=.36).11 Results of ALND and 1% for those who did not.12 Results of this
the ACOSOG Z0011 trial show that ALND is not trial show that in patients with only micrometastases
needed in women with early-stage breast cancer who in the SLNs, ALND is not needed.
have only 1 or 2 SLN metastases who will receive The results of a trial by the European EORTC
WBRT as part of breast-conserving therapy. group (AMAROS) assessed whether axillary ra-
Another randomized trial (IBCSG 23-01) was diation therapy (RT) provides regional control with
specifically designed to compare outcomes in patients fewer side effects compared with ALND.13 This
with sentinel micrometastases (≤2 mm) treated with trial included patients (n=4,823) with T1 or T2
ALND versus no ALND.12 Although the ACOSOG breast cancer and positive SLNs (micrometastatic
Z0011 trial was limited to those undergoing breast- or macrometastatic), and included a small fraction
conserving therapy, this trial included patients under- of patients (n=248) treated with mastectomy.13 The
going mastectomy (9%).12 No differences were seen in results reported no difference in 5-year OS or DFS for
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Version 1.2017 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any
form without the express written permission of NCCN®.
BINV-6
patients randomized to ALND versus axillary RT.13 with biopsy-proven axillary metastases. Traditional
The 5-year DFS was 86.9% (95% CI, 84.1–89.3) in level I and II ALND requires that ≥10 lymph nodes
the ALND group and 82.7% (95% CI, 79.3–85.5) be provided for pathologic evaluation to accurately
in the axillary RT group. The 5-year OS was 93.3% stage the axilla.15,16 ALND should be extended to
(95% CI, 91.0–95.0) in the ALND group and 92.5% include level III nodes only if gross disease is appar-
(95% CI, 90.0–94.4) in the axillary RT group.13 At ent in the level II and III nodes. In the absence of
the end of 5 years, lymphedema was less frequent in gross disease in level II nodes, lymph node dissec-
the group treated with axillary RT versus ALND (11% tion should include tissue inferior to the axillary
vs 23%).13 The results of this trial show that axillary vein from the latissimus dorsi muscle laterally to the
RT is an acceptable alternative to ALND for axillary medial border of the pectoralis minor muscle (level I
control in patients found to have positive SLNs, with and II) (see BINV-D; page 440).
significantly less lymphedema-related morbidity. If axillary lymph nodes are clinically negative
at diagnosis or if FNA/core biopsy results of suspi-
NCCN Recommendations cious nodes are negative, the panel recommends
In patients with clinically positive nodes, to deter- SLN mapping and excision. SLNs can be assessed
mine whether ALND is needed, the panel recom- for the presence of metastases by both hematoxylin-
mends pathologic confirmation of malignancy using eosin (H&E) staining and cytokeratin immunohis-
ultrasound-guided fine-needle aspiration (FNA)14 or tochemistry (IHC). The clinical significance of a
core biopsy of suspicious nodes. According to the lymph node that is negative on H&E staining but
NCCN panel, the recommendation for axillary dis- positive on cytokeratin IHC is not clear. Because the
section of level I and II nodes is limited to patients historical and clinical trial data on which treatment
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ER-positive
Follow appropriate
and/or
pathway above
PR-positive
ER-negative
Repeat determination
and
of ER/PR status
PR-negative
ER-negative Treat as usual breast cancer
and histology
PR-negative (See BINV-7 and BINV-8)
xConsider adjuvant bisphosphonate therapy in postmenopausal (natural or induced) suggest that sequential or concurrent endocrine therapy with radiation therapy is
patients receiving adjuvant endocrine therapy. acceptable. See Adjuvant Endocrine Therapy (BINV-J) and Preoperative/Adjuvant
yEvidence supports that the magnitude of benefit from surgical or radiation ovarian Therapy Regimens (BINV-K).
ablation in premenopausal women with hormone receptor-positive breast cancer is aaThere are limited data to make chemotherapy recommendations for those >70 y
similar to that achieved with CMF alone. See Adjuvant Endocrine Therapy (BINV-J). of age. See NCCN Clinical Practice Guidelines for Older Adult Oncology.
zChemotherapy and endocrine therapy used as adjuvant therapy should be given
sequentially with endocrine therapy following chemotherapy. Available data
Version 1.2017 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any
form without the express written permission of NCCN®.
BINV-9
decisions are based have relied on H&E staining, the panel recommends no ALND for patients with posi-
panel does not recommend routine cytokeratin IHC tive SLNs when disease is only micrometastatic (see
to define node involvement and believes that cur- BINV-D; page 440). According to AJCC staging,
rent treatment decisions should be made based solely micrometastatic nodal involvement is defined as a
on H&E staining. This recommendation is further metastatic deposit >0.2 mm but ≤2.0 mm.18
supported by a randomized clinical trial (ACOSOG When SNLs are not successfully identified, the
Z0010) for patients with H&E-negative nodes in panel recommends level I and II axillary dissection
whom further examination by cytokeratin IHC was be performed for axillary staging.
not associated with improved OS over a median of For mastectomy patients with clinically nega-
6.3 years.17 In the uncommon situation in which tive axillae but with positive SLNs, the panel notes
H&E staining is equivocal, reliance on the results of that for regional control of disease, axillary RT may
cytokeratin IHC is appropriate. replace ALND (see BINV-D; page 440).
Based on the ACOSOG Z0011 trial results, for
patients with T1 or T2 tumors and 1 to 2 positive
SLNs, treated with lumpectomy but no preopera- Adjuvant RT for Stages I, IIA,
tive systemic therapy, and who receive WBRT, the IIB, and IIIA (T3N1M0)
NCCN panel recommends no further axillary sur-
Adjuvant RT After Lumpectomy
gery. If any of these criteria are not met, the panel
recommends level I and II axillary dissection. In Whole-Breast Radiation Therapy: WBRT reduc-
the 2017 version of the NCCN Guidelines, based es the risk of local recurrence and has been shown
on the results of the IBCSG 23-01 trial, the NCCN to have a beneficial effect on survival. Results of a
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SURGICAL AXILLARY STAGING - STAGE I, IIA, IIB and lllA T3, N1, M0
Version 1.2017 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any
form without the express written permission of NCCN®.
BINV-D
meta-analysis by the Early Breast Cancer Trialists’ radiation-related effects to normal breast tissue,
Collaborative Group (EBCTCG) showed reduction such as breast shrinkage, telangiectasia, and breast
in 10-year risk of recurrence in those who received edema, were less common with the hypofractionated
WBRT versus those who did not (19% vs 35%; rela- fraction regimen.24
tive risk [RR], 0.52; 95% CI, 0.48–0.56).19 In addi- RT Boost to the Tumor Bed: Randomized trials
tion, a significant reduction in 15-year risk of breast have demonstrated a reduction in local recurrence
cancer death (21% vs 25%; RR, 0.82; 95% CI, 0.75– with the addition of a boost to the tumor bed in pa-
0.90) was also observed.19 tients with higher-risk characteristics (eg, age <50
Dose and Fractionation: The conventional dose for years, high-grade disease, or focally positive mar-
WBRT is 46 to 50 Gy in 23 to 25 fractions. Four gins).24–30 Boost treatment may be delivered using
randomized clinical trials including more than 7,000 photons, electrons, or brachytherapy.
patients have investigated hypofractionated WBRT NCCN Recommendations for WBRT With or
schedules (39–42.9 Gy in daily fractions of 2.6–3.3 Without Boost to Tumor Bed: After breast-conserv-
Gy) compared with standard 50 Gy doses in frac- ing surgery, WBRT is recommended with or without
tions of 2 Gy.20–23 The 10-year follow-up data from a boost to the tumor bed (category 1). The panel
the START trials24 are consistent with the 10-year recommends that WBRT include the breast tissue
results of the Canadian trial,23 which reported at in its entirety. CT-based treatment planning is rec-
least equivalent local tumor control and breast cos- ommended to assure adequate target coverage of the
mesis between both conventional and hypofraction- breast tissue and lumpectomy site and limit dose to
ated regimens.23 The START trials reported that normal tissues, especially the heart and lungs.
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Version 1.2017 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any
form without the express written permission of NCCN®.
BINV-J
Compensators such as tissue wedges, forward RNI After Lumpectomy: RNI includes treatment
planning using segments, and intensity-modulated of the supraclavicular, infraclavicular nodes, axillary
RT (IMRT) may provide improved homogeneity of bed at risk, and internal mammary nodes.
target dose and normal tissue sparing.31,32 Treatment Use of RNI was shown to reduce risk of locore-
techniques such as respiratory control using deep gional and distant recurrence and improve DFS in
inspiration breath-hold and prone positioning can the MA.20 and EORTC 22922/10925 trials.34,35 In
further reduce dose to adjacent normal tissues, par- the MA.20 trial, women (n=1,800) who had under-
ticularly the heart and lungs.33 gone lumpectomy were randomly assigned to WBRT
with or without RNI. An improvement in 10-year
The NCCN panel recommends a dose of 46
DFS was seen with the addition of regional RT com-
to 50 Gy in 23 to 25 fractions or 40 to 42.5 Gy in
pared with WBRT alone (82% vs 77%; hazard ratio
15 to 16 fractions for WBRT. Based on the results
[HR], 0.76; 95% CI, 0.61–0.94). Distant recurrences
from the Canadian and START trials and over-
were reduced from 17.3% to 13.4% in those receiv-
all convenience, hypofractionated courses are the ing WBRT alone versus those who also received
NCCN-preferred option for treating patients receiv- RNI.35 No improvement was seen in 10-year OS with
ing WBRT. Use of hypofractionation is not recom- the addition of RNI compared with WBRT alone
mended for RNI. A boost to the tumor bed is recom- (82.8% vs 81.8%; HR, 0.91; 95% CI, 0.72–1.13).
mended in patients with higher-risk characteristics In the EORTC 22922/10925 trial, women
(eg, age <50 years, high-grade disease, or focally (n=4,000) were treated with lumpectomy plus
positive margins). Typical boost doses are 10 to 16 WBRT or mastectomy plus chest wall radiation
Gy in 4 to 8 fractions. (n=955) and were randomly assigned to radiation
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Postmenopausal Patients
• Non-steroidal aromatase inhibitor (anastrozole, letrozole)
• Steroidal aromatase inactivator (exemestane)
• Exemestane + everolimus1,2
• Palbociclib + letrozole (category 1)2,3
• Palbociclib + fulvestrant (category 1)4
• Selective ER down-regulator (fulvestrant)5
• Tamoxifen or toremifene
• Megestrol acetate
• Fluoxymesterone
• Ethinyl estradiol
Version 1.2017 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any
form without the express written permission of NCCN®.
BINV-N
to the internal mammary and medial supraclavicular cancers irrespective of lymph node involvement, of
nodes or no RNI.34 At a median follow-up of 10.9 which 44.4% (n=1,778) were node-negative. DFS in
years, the addition of RNI resulted in a significant patients who received RNI was 76% versus 72% in
reduction in breast cancer mortality compared with those who did not (HR, 0.85; 95% CI, 0.70–1.02).34
no additional treatment (12.5% vs 14.4%; HR, 0.82;
NCCN Recommendations for RNI After Lumpec-
95% CI, 0.70–0.97). An improved was seen in DFS
as well (72.1% vs 69.1%; HR, 0.89; 95% CI, 0.80– tomy: For patients with ≥4 positive lymph nodes,
1.00; P=.04). the NCCN panel recommends RNI to the supracla-
Both the MA.20 and EORTC 22922/10925 tri- vicular and infraclavicular areas, internal mammary
als included patients with high-risk, node-negative nodes, and any part of the axillary bed at risk (cate-
disease.34,35 In MA.20, patients with high-risk node- gory 1). For those with 1 to 3 positive axillary nodes,
negative disease (n=177; 10% of total enrolled) the panel recommends strong consideration of RNI
included those with a primary tumor measuring ≥5 to these areas (category 2A).
cm, or ≥2 cm with <10 axillary nodes removed, and RNI for patients with negative axillary nodes is
at least one of the following: grade 3 histology, ER not routinely recommended by the panel. However
negativity, or lymphovascular invasion (LVSI). For in patients with central/medial primary tumors or
those with high-risk, node-negative disease, the tumors >2 cm with other high-risk features such as
10-year DFS was 83.7% with WBRT plus RNI ver- young age or extensive LVSI, according to the up-
sus 72.4% with WBRT alone (HR, 0.55; 95% CI, dated NCCN Guidelines, RNI may be considered on
0.28–1.09).35 The EORTC study eligibility included the basis of assessed individual risk for locoregional
patients with stage I, II, III central/medial breast recurrence. The guidelines updates reflect these
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Project phase III protocol B-32. J Clin Oncol 2010;28:3929–3936.
1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin
2017;67:7–30. 7. Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of
sentinel node biopsy versus standard axillary treatment in operable breast
2. Deutsch M, Land S, Begovic M, Sharif S. The incidence of arm edema in
women with breast cancer randomized on the National Surgical Adjuvant cancer: the ALMANAC Trial. J Natl Cancer Inst 2006;98:599–609.
Breast and Bowel Project study B-04 to radical mastectomy versus total 8. Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of
mastectomy and radiotherapy versus total mastectomy alone. Int J Radiat sentinel-node biopsy with routine axillary dissection in breast cancer. N
Oncol Biol Phys 2008;70:1020–1024. Engl J Med 2003;349:546–553.
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