This document summarizes a presentation on breast cancer treatment. It discusses:
1) The current state of breast cancer treatment including molecular classification, adjuvant therapies, neoadjuvant therapies, and treatments for metastatic disease.
2) Surgical options for breast cancer including lumpectomy, mastectomy, and breast reconstruction techniques.
3) Radiation therapy techniques including reducing heart dose using deep inspiration breath hold and shorter treatment schedules.
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Breast Cancer Treatment: Where we are, Where we're going - April 24th, 2018
1. Breast Cancer Treatment:
Where We Are, Where Weâre Going
Presented by:
Lisa A. Mills, MD
Winnie M. Polen, DO
David Schreiber, MD
April 24, 2018
2. 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 Centerâs 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.
3. Summit Medical Group MD Anderson Cancer Center
Cancer services include:
⢠Breast Care Center
⢠Hematology and Oncology
⢠Infusion Center
⢠Gynecologic Oncology
⢠Radiation Oncology
⢠Surgical Oncology
4. Biology of Breast Cancer
Lisa A. Mills, MD
Board-certified oncologist and hematologist
7. 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
8. 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
9. Pathologic Prognostic Stage
⢠AJCC, 8th edition
ď˝ TNM
ď˝ Grade of tumor
ď˝ HER 2 status
ď˝ ER status
ď˝ PR status
ď˝ Oncotype Dx Score is less than 11
⢠TNM T1, T2 N0, M0
⢠Any grade, Her 2 negative, ER positive, PR Any Stage IA
10. Molecular Classification of
Breast Cancer
⢠Molecular profiling based on protein gene
expression profiles
ď˝ Luminal A (ER +, PR +, Her 2 negative, Ki 67 low)
ď˝ Luminal B (ER +, PR +, Her 2 +/-, Ki 67 varies)
ď˝ Her 2 positive (ER -, PR -, Her 2 +)
ď˝ Basal like ( ER -, PR -, Her 2 -)
14. 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
16. ER positive, HER2 negative
⢠Not all patients benefit from chemotherapy
⢠Paik et al, 2004 prospective analysis of NSABP
14 trial
⢠Oncotype Dx Assay
ď˝ Measures simultaneous expression of multiple genes
ď˝ Performed on formalin fixed, paraffin embedded
breast tissue
17. Oncotype Dx
⢠Useful in ER positive, HER2 negative, 2 mm <
lymph node positive breast cancer
ď˝ Low recurrence score â prognosis is favorable that
tamoxifen alone is sufficient
ď˝ High recurrence score- prognosis is sufficiently
unfavorable that chemotherapy is recommended
ď˝ Intermediate score â benefit of chemotherapy
uncertain
18. Panel of 21 Genes in Recurrence
Score Algorithm
21. Treatment in Metastatic ER Positive
Breast Cancer
⢠Everolimus (Afinitor)
⢠Palbociclib (Ibrance)
⢠Ribociclib (Kisqali)
⢠Abemaciclib (Verzenio)
⢠Phosphatydinositol 3 kinase
22. Treatment of High Grade Tumors
⢠Her 2 positive
ď˝ Neoadjuvant
ď˝ Adjuvant
ď˝ Metastatic
⢠Triple Negative breast cancer
ď˝ Neoadjuvant
ď˝ Metastatic
ď˝ BRCA positive
23. 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
25. 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
27. 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
29. 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
31. 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
33. 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
35. 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
36. Triple Negative Breast Cancer
⢠Originate from basal epithelial layer of mammary
ducts
ď˝ 5-7% of all ductal carcinoma
ď˝ More aggressive
ď˝ do not respond to hormonal therapy
ď˝ more commonly seen in younger women
ď˝ Studies looking at alternative chemotherapy
37. Triple Negative Breast Cancer
⢠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
38. 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
40. Triple Negative Breast Cancer
⢠Pembrolizumab (Keytruda)
ď˝ Programmed death receptor 1 blocking
antibody
ď˝ Early studies in metastatic triple negative
breast cancer show over all response rate
20%
ď˝ On going Phase III studies for inoperable/
metastatic triple negative breast cancer of
placebo and chemotherapy versus
Pembrolizumab/chemotherapy
42. Surgical Options for
Breast Cancer Treatment
Winnie M. Polen, DO
Board-certified breast surgeon specializing in diagnosing and managing
benign and malignant breast conditions.
45. BREAST RECONSTRUCTION
⢠Purpose
ď˝ Restore the contour of your breasts
ď˝ Restore your self confidence
⢠Goal
ď˝ Symmetry
⢠Generally covered by insurance due to cancer
diagnosis
50. 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 patientsâ 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.
51. NEWER TECHNIQUES / ADVANCES
⢠Laser Therapy
ď˝ BR-002: A Multicenter âAblate and Resectâ Study of Novilase
Interstitial Laser Therapy for the Ablation of Small Breast
Cancers
ď˝ Enrollment Complete â April 2015
ď˝ Evaluate the rate of complete tumor ablation (destruction by laser)
of breast cancers that are less than or equal to 2 centimeters.
52. 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 â¤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.
54. What is external beam radiation?
⢠Targeted x-rays at
a precise, defined
area
⢠Invisible, painless
⢠You are NOT
radioactive
55.
56. 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!
58. 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
59. Why RT for DCIS
⢠Several randomized studies have proven that radiation therapy
reduces the risk of recurrence
ď˝ EBCTCG: 10 year local recurrence of 12.9% for RT versus
28.1% with surgery alone
ď˝ Roughly half of these recurrences were invasive cancers
60. RT works even better with Tamoxifen
Surgery +
RT
Surgery +
RT +
tamoxifen
Surgery
alone
61. Why RT after Lumpectomy?
~3 fold reduction in recurrence
62. Why RT after Mastectomy?
~ 3 fold reduction in recurrence
63. Why RT after Mastectomy
10% improvement in survival
64. Reducing local recurrence improves
survival
⢠EBCTCG Meta-analysis rules of thumb:
⢠After lumpectomy:
ď˝ 10,801 women
ď˝ For every 4 recurrences reduced at 10 years = 1 life saved
from breast cancer death at 15 years
⢠After mastectomy (with positive nodes):
ď˝ 8,135 women
ď˝ For every 2-2.5 recurrences reduced at 10 years= 1 life
saved at 15 years
66. Omitting RT
⢠Princess Margaret
ď˝ Age âĽ50
ď˝ T1-T2
5 yrs 8yrs
RT 0.6% 3.5%
No RT 7.7% 17.6%
67. Omitting RT
⢠CALGB 9343
ď˝ Age âĽ70
ď˝ T1N0
10 years LR OS Mastectomy
free survival
Tam 10% 66% 96%
Tam + RT 2% 67% 98%
68. Omitting RT
⢠PRIME II
ď˝ Age âĽ65
ď˝ T1-2 (â¤3cm)
5 year results
LR OS
No RT 4.1% 93.8%
RT 1.3% 94.2%
69. Omitting RT for DCIS
⢠RTOG 9804
ď˝ <2.5cm
ď˝ Low/intermediate
grade
5 years 7 years
No RT 3.5% 6.7%
RT 0.4% 0.9%
70. Omitting RT for DCIS (2)
⢠ECOG 5194
ď˝ Low risk similar to RTOG
ď˝ 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%
71. Oncotype DCIS from ECOG
⢠Uses 12/21 genes from
Oncotype DX
⢠Score of 0-100
ď˝ Low: <39
ď˝ Int: 39-54
ď˝ High: >54
Most (>80%) of these
patients had âlow riskâ
72. Conclusions
⢠There may be a role for omission of RT in select settings.
⢠But still needs to be better definedâŚ
ď˝ Increased longevity redefining the word âolderâ
ď˝ Better systemic therapy making local control more important
ď˝ New modalities to shorten and reduce the intensity of therapy
ď˝ Utilization of gene recurrence scores in the future
73. How have we improved?
1.Reduced heart dosing
2.Faster treatments
3.Smaller treatment areas
77. Faster treatment schedules
⢠Historical creed was low dose, long treatment schedules
ď˝ 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
ď˝ MD Anderson, Canadian, Royal Marsden, UK X 2
⢠No difference
ď˝ 15-22 daily treatments 3-4weeks
78. Faster treatment schedules in the USA
⢠Summit Medical Group MD Anderson Cancer Center
ď˝ Has been utilized on >95% of eligible women
⢠United States has been much slower on the uptake
ď˝ National Cancer Database 2013:
⢠13.4% of women in one study
⢠18.2% in the other
ď˝ University of Pittsburgh: women >70= 33.8%
ď˝ Michigan Consortium: 31%
ď˝ Medicare report: 18.9%
79. 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
80. Why has the rest of the country been
slow to change?
⢠âSacrifice a little
profitability to do
the right thing for
the patientâ
-Jeffrey Le Benger CEO Summit Medical Group
82. Partial Breast Radiation
⢠GEC-ESTRO
ď˝ Brachytherapy
⢠TARGIT and ELIOT
ď˝ Intraoperative radiation
⢠IMPORT and OPAL
ď˝ 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%
83. MD Anderson OPAL Trial
⢠Builds off of recent IMPORT Low study
ď˝ T1-2N0-1, âĽ2mm margins breast cancer received either whole
breast radiotherapy or partial breast radiotherapy in 3 weeks.
ď˝ No difference in outcomes at 5 years
ď˝ Recurrence ~1% at 5 years
ď˝ Same or better cosmesis in partial breast patients
84. MD Anderson OPAL Trial
⢠Opal:
ď˝ Designed by Benjamin Smith MD- author of the national
radiotherapy guidelines for whole breast and partial breast
radiation.
ď˝ Reduces treatment time to 2 weeks
ď˝ Includes patients who after lumpectomy have close margins
â¤2mm
85. 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
86. Other changes on the horizonâŚ.
⢠Maturation of the partial breast radiation data
⢠Short course schedules for women even post-mastectomy
⢠Identifying women in whom radiation can be withheld safely
ď˝ Gene testing, based on response to chemotherapy
⢠Identifying how best to address nipple-sparing mastectomy
⢠Incorporation of immunotherapy with radiation