Breast Cancer Treatment: Where we are, Where we're going - April 24th, 2018

Breast Cancer Treatment:
Where We Are, Where We’re Going
Presented by:
Lisa A. Mills, MD
Winnie M. Polen, DO
David Schreiber, MD
April 24, 2018

The Partnership
Summit Medical Group MD Anderson Cancer Center offers cancer patients in
Northern New Jersey access to cancer treatments that are among the most advanced in the nation.
Our experts adhere to the multi-disciplinary care, treatment innovations and standards of care of
MD Anderson Cancer Center’s clinical leadership and provide a full range of cancer services,
including medical oncology, surgery and radiation. We offer leading oncology services covering all
aspects of patient care, from routine screenings, diagnostics, treatment and surgery to survivorship in
Berkeley Heights, Morristown and Florham Park.
New Radiation Oncology
Department in
Berkeley Heights
Artist rendering of Florham Park facility.

Summit Medical Group MD Anderson Cancer Center
Cancer services include:
• Breast Care Center
• Hematology and Oncology
• Infusion Center
• Gynecologic Oncology
• Radiation Oncology
• Surgical Oncology

Biology of Breast Cancer
Lisa A. Mills, MD
Board-certified oncologist and hematologist

Overview
• Background
• Classification
• Pathologic staging
• Biological subtypes
• Treatment
• Neoadjuvant
• Adjuvant
• Metastatic

Background
• Leading cause of cancer death in women worldwide
• In the U.S., breast cancer is the second most
common cause of cancer death among women (after
lung cancer)
• Approximately 266,000 women will be diagnosed
with the disease in the U.S.
• Women in the U.S. have a 1 in 8 lifetime chance of
developing invasive breast cancer and a 1 in 33
chance of breast cancer causing their death

Invasive Breast Cancer
• Infiltrating ductal - 70-80%
• Invasive lobular 5-10%
• Tubular 10-20%
• Medullary 5-10%
• Mucinous colloid 1-2%
• Papillary-1-2%
• Other 1-2%
Netter, 1989

Pathologic Prognostic Stage
• AJCC, 8th edition
 TNM
 Grade of tumor
 HER 2 status
 ER status
 PR status
 Oncotype Dx Score is less than 11
• TNM T1, T2 N0, M0
• Any grade, Her 2 negative, ER positive, PR Any Stage IA

Molecular Classification of
Breast Cancer
• Molecular profiling based on protein gene
expression profiles
 Luminal A (ER +, PR +, Her 2 negative, Ki 67 low)
 Luminal B (ER +, PR +, Her 2 +/-, Ki 67 varies)
 Her 2 positive (ER -, PR -, Her 2 +)
 Basal like ( ER -, PR -, Her 2 -)

Breast Cancer Begins in Cells Within
the Terminal Ducts

The Intrinsic Gene Set Assorts Tumor Samples
into
Biologically Relevant Groups
HER2
????
Basal
Normal
Luminal

Prognosis and Subtypes
Am J Cancer Res. 2015; 5(10):
2929–2943.

Treatment of Better Prognosis Subtypes
• Adjuvant therapy for low grade ER + tumor
• Retrospective analysis more benefit chemo in
patients that are not highly ER positive as
opposed to those that are
• Can we tailor treatment and prevent future
cardiac toxicity and leukemic risk
• Oncotype

Adjuvant Hormonal Therapy
NEJM

ER positive, HER2 negative
• Not all patients benefit from chemotherapy
• Paik et al, 2004 prospective analysis of NSABP
14 trial
• Oncotype Dx Assay
 Measures simultaneous expression of multiple genes
 Performed on formalin fixed, paraffin embedded
breast tissue

Oncotype Dx
• Useful in ER positive, HER2 negative, 2 mm <
lymph node positive breast cancer
 Low recurrence score – prognosis is favorable that
tamoxifen alone is sufficient
 High recurrence score- prognosis is sufficiently
unfavorable that chemotherapy is recommended
 Intermediate score – benefit of chemotherapy
uncertain

Panel of 21 Genes in Recurrence
Score Algorithm

Treatment in Metastatic ER Positive
Breast Cancer
• Everolimus (Afinitor)
• Palbociclib (Ibrance)
• Ribociclib (Kisqali)
• Abemaciclib (Verzenio)
• Phosphatydinositol 3 kinase

Treatment of High Grade Tumors
• Her 2 positive
 Neoadjuvant
 Adjuvant
 Metastatic
• Triple Negative breast cancer
 Neoadjuvant
 Metastatic
 BRCA positive

HER 2 Oncogene
• Over expressed in 18 to 20% of breast cancer
• 185 kD transmembrane glycoprotein receptor
intracellular tyrosine kinase activity
• ERBB-2, HER2/neu, EGFR 2

Importance of HER2 Recognition
• Higher rates of disease recurrence and death.
• ? Resistance to endocrine therapy
• Increased sensitivity to certain chemotherapy
agents
• Target therapy against HER2

Trastuzumab (Herceptin)
Humanized monoclonal antibody
Treatment in Neoadjuvant setting with
pertuzumab for tumors > 2 cm or lymph node
positive
Treatment for Adjuvant therapy for Her 2
positive breast cancer
Metastatic setting with Taxane

Mechanism of Action
Contemporary
Oncology, 2014

Pertuzumab (Perjeta)
Recombinized monoclonal antibody the inhibits the
extracellular domain of HER 2 protein
Used in combination with Trastuzumab for
Neoadjuvant therapy > 2cm tumor or lymph node
positive
Metastatic setting with Taxane

Ado-trastuzumab emtansine
(Kadcyla)
• Her 2 antibody drug conjugate
• Humanized antiHer 2 IgG1 trastuzumab
linked to microtubule inhibitory drug DM1
• Second line therapy after progressed on
Taxane, Trastuzumab and pertuzumab

Lapatinib
• Inhibitor of tyrosine kinase domains of HER 2.
• Used in combination with Capecitabine
• Indicated after progression after Trastuzumab,
Anthracycline and Taxane
• Small molecule crosses blood brain barrier

Neratinib
• Inhibitor of tyrosine kinase domain
irreversible binds to EGFR, HER 2 and
HER4
• For extended adjuvant therapy after
Trastuzumab/Pertuzumab
• Daily oral tablet for one year
• Significant side effect of diarrhea

Triple Negative Breast Cancer
• Originate from basal epithelial layer of mammary
ducts
 5-7% of all ductal carcinoma
 More aggressive
 do not respond to hormonal therapy
 more commonly seen in younger women
 Studies looking at alternative chemotherapy

• Alliance trial found increased response rates in
patients that received Carboplatin for
Neoadjuvant therapy
• In this population, 20 % BRCA positive, respond
to Carboplatin
• Capecitabine used as adjuvant therapy after
preoperative chemotherapy

PARP Inhibitors
• Polyadenosine diphosphate polymerase 1
(PARP) is a regulator of DNA base excision
repair
• BRCA 1 positive in 15 to 20 % of breast cancer
and dependent on PARP for cell division
• Olaparib (Lynparza) treatment for germline
BRCA mutation after treatment with
chemotherapy

• Pembrolizumab (Keytruda)
 Programmed death receptor 1 blocking
antibody
 Early studies in metastatic triple negative
breast cancer show over all response rate
20%
 On going Phase III studies for inoperable/
metastatic triple negative breast cancer of
placebo and chemotherapy versus
Pembrolizumab/chemotherapy

Future
Biology triumphs anatomy in the
determination of the prognosis and
treatment of breast cancer

Surgical Options for
Breast Cancer Treatment
Winnie M. Polen, DO
Board-certified breast surgeon specializing in diagnosing and managing
benign and malignant breast conditions.

SURGICAL OPTIONS
• Lumpectomy
 Wire localized
• Mastectomy
• Breast Reconstruction

NIPPLE SPARING MASTECTOMY
IMF Radial Periareolar Vertical

BREAST RECONSTRUCTION
• Purpose
 Restore the contour of your breasts
 Restore your self confidence
• Goal
 Symmetry
• Generally covered by insurance due to cancer
diagnosis

• Options
 Implants
 Autologous tissue

• How many steps?
 Varies between 1 to several surgeries
• Patient satisfaction?

Breast Reconstruction Post Mastectomy:
Patient Satisfaction and Decision Making
Hunter-Smith, David J. MBBS(Hons), FRACS et al.
Annals of Plastic Surgery: June 2016 Vol 76 Issue 6 p 640-644
• Methods: Retrospective cohort study (296 consecutive mastectomy
patients from 2000 to 2010) uses an internationally validated
questionnaire (BREAST-Q) to evaluate patients’ satisfaction
• Results: 219 patients responded (74%). 143 patients who elected to
participate, 79 had reconstruction and 64 had no-reconstruction group.
Patient demographics and cancer variables were matched.
• The reconstruction group showed statistically higher BREAST-Q scores
with regard to satisfaction with the breast (P < 0.0001), psychological
well-being (P = 0.0068), and sexual well-being (P = 0.0001).
• For the reconstruction group, the main reasons for undergoing
reconstruction included improved self-image, more clothing choices,
and the feeling of overcoming the cancer.

NEWER TECHNIQUES / ADVANCES
• Laser Therapy
 BR-002: A Multicenter “Ablate and Resect” Study of Novilase
Interstitial Laser Therapy for the Ablation of Small Breast
Cancers
 Enrollment Complete – April 2015
 Evaluate the rate of complete tumor ablation (destruction by laser)
of breast cancers that are less than or equal to 2 centimeters.

NEWER TECHNIQUES / ADVANCES
• Cryotherapy
• A Phase II Trial Exploring the Success of Cryoablation Therapy
in the Treatment of Invasive Breast Carcinoma: Results from
ACOSOG (Alliance) Z1072. Simmons et al
• METHODS: Eligible patients = unifocal invasive ductal breast
cancer ≤2 cm, with <25 % intraductal component and tumor
enhancement on MRI. A total of 19 centers contributed 99 patients,
of which 86 patients (87 breast cancers) were evaluable
for analysis.
• RESULTS: Final pathology results showed successful ablation in
66/87 (75.9 %) cancers. When multifocal disease outside of the
targeted cryoablation zone was not defined as an ablation failure,
80/87 (92 %) of the treated cancers had a successful cryoablation.

Radiation Oncology Treatment for
Breast Cancer
David Schreiber, MD
Board-certified radiation oncologist

What is external beam radiation?
• Targeted x-rays at
a precise, defined
area
• Invisible, painless
• You are NOT
radioactive

Potential side effects
Short term
• Fatigue (usually mild)
• Skin
Long term
• Cosmesis
• Lungs
• Heart
• Secondary malignancy
• Lymphedema
We will review what we are doing to reduce some of
these!

Principles of Breast Conservation
Therapy (BCT)
1. Remove bulk of tumor surgically
2. RT to eradicate residual disease
3. Minimize debilitating effects of radical
surgery
4. Improves cosmesis

Why RT for DCIS
• Several randomized studies have proven that radiation therapy
reduces the risk of recurrence
 EBCTCG: 10 year local recurrence of 12.9% for RT versus
28.1% with surgery alone
 Roughly half of these recurrences were invasive cancers

RT works even better with Tamoxifen
Surgery +
RT
Surgery +
RT +
tamoxifen
Surgery
alone

Why RT after Lumpectomy?
~3 fold reduction in recurrence

Why RT after Mastectomy?
~ 3 fold reduction in recurrence

Why RT after Mastectomy
10% improvement in survival

Reducing local recurrence improves
survival
• EBCTCG Meta-analysis rules of thumb:
• After lumpectomy:
 10,801 women
 For every 4 recurrences reduced at 10 years = 1 life saved
from breast cancer death at 15 years
• After mastectomy (with positive nodes):
 8,135 women
 For every 2-2.5 recurrences reduced at 10 years= 1 life
saved at 15 years

Omitting RT
2 older studies and 2 newer studies
• NSABP-21
 T1N0
17%
9%
3%

Omitting RT
• Princess Margaret
 Age ≥50
 T1-T2
5 yrs 8yrs
RT 0.6% 3.5%
No RT 7.7% 17.6%

Omitting RT
• CALGB 9343
 Age ≥70
 T1N0
10 years LR OS Mastectomy
free survival
Tam 10% 66% 96%
Tam + RT 2% 67% 98%

Omitting RT
• PRIME II
 Age ≥65
 T1-2 (≤3cm)
5 year results
LR OS
No RT 4.1% 93.8%
RT 1.3% 94.2%

Omitting RT for DCIS
• RTOG 9804
 <2.5cm
 Low/intermediate
grade
5 years 7 years
No RT 3.5% 6.7%
RT 0.4% 0.9%

Omitting RT for DCIS (2)
• ECOG 5194
 Low risk similar to RTOG
 High risk allowed 1cm high
grade tumors 5 years 7 years 10 years 12 years
Low risk 6% 9.5% 12.5% 14.4%
High risk 15% 18.2% 24.6% 24.6%

Oncotype DCIS from ECOG
• Uses 12/21 genes from
Oncotype DX
• Score of 0-100
 Low: <39
 Int: 39-54
 High: >54
Most (>80%) of these
patients had “low risk”

Conclusions
• There may be a role for omission of RT in select settings.
• But still needs to be better defined…
 Increased longevity redefining the word “older”
 Better systemic therapy making local control more important
 New modalities to shorten and reduce the intensity of therapy
 Utilization of gene recurrence scores in the future

How have we improved?
1.Reduced heart dosing
2.Faster treatments
3.Smaller treatment areas

Reduced heart dose:
Deep inspiration breath hold
• Minimal training
• Easy to learn

Deep Inspiration Breath Hold Training at
Summit Medical Group
MD Anderson Cancer Center

It actually is easy (and pretty cool)

Faster treatment schedules
• Historical creed was low dose, long treatment schedules
 33-35 daily treatments ~7 weeks
• Multiple trials have now shown with long term follow up that
shorter schedules are equivalent or better in outcomes and
cosmesis
 MD Anderson, Canadian, Royal Marsden, UK X 2
• No difference
 15-22 daily treatments 3-4weeks

Faster treatment schedules in the USA
• Summit Medical Group MD Anderson Cancer Center
 Has been utilized on >95% of eligible women
• United States has been much slower on the uptake
 National Cancer Database 2013:
• 13.4% of women in one study
• 18.2% in the other
 University of Pittsburgh: women >70= 33.8%
 Michigan Consortium: 31%
 Medicare report: 18.9%

Why have we exceeded National
performance?
• Because this is the essence of the MD Anderson standard and the
Summit Medical Group quality
1. MD Anderson guideline based treatment
2. Review of all radiation plans by MD Anderson Breast specialist
3. Implementation of MD Anderson trials
4. Summit Medical Group MD Anderson Multi-disciplinary clinics &
tumor boards
5. Unique closeness among Summit Medical Group physicians

Why has the rest of the country been
slow to change?
• “Sacrifice a little
profitability to do
the right thing for
the patient”
-Jeffrey Le Benger CEO Summit Medical Group

Smaller treatment areas- Partial breast

Partial Breast Radiation
• GEC-ESTRO
 Brachytherapy
• TARGIT and ELIOT
 Intraoperative radiation
• IMPORT and OPAL
 External beam radiation
Partial Whole
Brachy 5 years 1.44% 0.92%
Intraop 5 years 3.3% 1.3%
Intraop 5.8 years 4.4% 0.4%
Ext beam 5 years 0.5% 1.1%

MD Anderson OPAL Trial
• Builds off of recent IMPORT Low study
 T1-2N0-1, ≥2mm margins breast cancer received either whole
breast radiotherapy or partial breast radiotherapy in 3 weeks.
 No difference in outcomes at 5 years
 Recurrence ~1% at 5 years
 Same or better cosmesis in partial breast patients

MD Anderson OPAL Trial
• Opal:
 Designed by Benjamin Smith MD- author of the national
radiotherapy guidelines for whole breast and partial breast
radiation.
 Reduces treatment time to 2 weeks
 Includes patients who after lumpectomy have close margins
≤2mm

MD Anderson OPAL
• Builds data towards a randomized trial comparing whole breast to
partial breast radiation
• Will be the stepping stone for changing the standard of care for
breast cancer
• Given the slow implementation of short courses of breast radiation
nationally, Summit Medical Group MD Anderson Cancer Center will
be at the forefront of this research

Other changes on the horizon….
• Maturation of the partial breast radiation data
• Short course schedules for women even post-mastectomy
• Identifying women in whom radiation can be withheld safely
 Gene testing, based on response to chemotherapy
• Identifying how best to address nipple-sparing mastectomy
• Incorporation of immunotherapy with radiation

Breast Cancer Treatment: Where we are, Where we're going - April 24th, 2018

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Breast Cancer Treatment: Where we are, Where we're going - April 24th, 2018