Annie Ellis, ovarian cancer survivor and research advocate, presented about research presented at the annual meeting.

1. AACR Report BackAACR Report Back
May 29, 2014May 29, 2014
Annie Ellis
Ovarian Cancer Survivor Advocate

2. 2014 AACR Report Back
Highlights from 2014 AACR Annual Meeting
AACR Scientist↔Survivor Program
◦ 5x5 Survey and Poster
Strategies for Dealing with Research Information

3. Annie Ellis
Ovarian and Breast Cancer Survivor
SHARE Helpline Peer
NY Presbyterian Woman to Woman
OCRF clinical trials video, symposium
OCNA research advocate, committees
CDMRP OCRP Integration Panel

4. Founded: 1907 by a group of 11 physicians and scientists
interested in research, "to further the investigation and
spread the knowledge of cancer."
Mission: To prevent and cure cancer through research,
education, communication, and collaboration.
The AACR fosters research in cancer and related biomedical
science; accelerates the dissemination of new research
findings among scientists and others dedicated to the
conquest of cancer; promotes science education and
training; and advances the understanding of cancer etiology,
prevention, diagnosis, and treatment throughout the world.
www.AACR.org

5. Targets and Targeted TherapiesTargets and Targeted Therapies
Opening Plenary: Harnessing Breakthroughs,
Targeting Cures
Recent advances in massively parallel sequencing have
made possible high throughput analysis of tumor
samples bringing targeted treatment strategies and
individualized medicine
Genomic basis for the heterogeneity of outcomes
Biomarkers driving trials
Personalized Medicine: The right individual, the right
care, the right time and the right place

6. Final Results PALOMAFinal Results PALOMA--1; TRIO1; TRIO--1818
Presentation Abstract
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=113bcbb9-585d-4939-
b5de-99e11e302ef2&cKey=54090e4a-2f25-4594-83b3-37e21e120e6b&mKey=6ffe1446-
a164-476a-92e7-c26446874d93
AACR in the News Article: Palbociclib Shows
Promising Results in Patients With Hormone
Receptor-positive Metastatic Breast Cancer
http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=3335
Phase II Ovarian Cancer palbociclib trial:
http://www.cancer.gov/clinicaltrials/search/view?cdrid=727128&version=HealthProfession
al&protocolsearchid=6378902

7. Two Faces of p53Two Faces of p53
Tumor Suppressor andTumor Suppressor and OncogeneOncogene
Presentation Abstract
http://www.abstractsonline.com/plan/ViewAbstract.aspx?mID=3404&sKey=113bcbb9-
585d-4939-b5de-99e11e302ef2&cKey=88d9c548-3f51-46c2-9da9-
7faafccbc7f3&mKey=6ffe1446-a164-476a-92e7-c26446874d93
Article in Genes & Development: P53: puzzle and
paradigm (Ko and Prives)
http://genesdev.cshlp.org/content/10/9/1054.full.pdf+html

8. Targets and Targeted TherapiesTargets and Targeted Therapies
Challenges:
Drivers and Passengers
Heterogeneity within tumors
Moving targets: DNA methylation, transcription
factors, dedifferentiation
Biomarker reproducibility
Incidentalomes

9. Vanderbilt
My Cancer Genome is a personalized cancer
medicine knowledge resource for physicians, patients,
caregivers and researchers.
My Cancer Genome gives up-to-date information on
what mutations make cancers grow and related
therapeutic implications, including available clinical
trials.
www.MyCancerGenome.org

10. MDAnderson
Functional proteomics represents a powerful approach to
rapidly improve understanding the pathophysiology and
therapy of cancer.
Currently contains 4,495 tumor samples from (i) TCGA
tumor tissue sample sets; (ii) independent tumor tissue
sample set; and (iii) >500 cell-line samples.
Provides a unique opportunity to validate the findings from
TCGA data and identify model cell lines for functional
investigation.
http://bioinformatics.mdanderson.org/main/TCPA:Overview

11. ImmunotherapyImmunotherapy
Phase I and II: Dramatic and durable responses of anti-PD-1 (MK-
3475) in heavily pre-treated melanoma and non-small cell lung
cancers expressing high levels of PD-L1. PD-1 on T cells attaches
to PD-L1 on tumors, activating PD-1 checkpoint (brake).
Abstracts
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3404&sKey=1a1f4fbb-
a45d-407f-861e-75f8d79db782&cKey=9c9fbd12-e5c1-43c0-9064-
87f04cb12932&mKey=6ffe1446-a164-476a-92e7-c26446874d93
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=1a1f4fbb-a45d-407f-861e-
75f8d79db782&cKey=875f683f-04fe-450a-a9cb-f51cac5436b8&mKey=6ffe1446-a164-
476a-92e7-c26446874d93
AACR in the News Article: Biomarker Identifies Melanoma
Patients Who May Respond to Immunotherapy MK-3475
http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=3307

12. ImmunotherapyImmunotherapy
Adoptive T-Cell Transfer Abstract
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=6770f171-dc66-40bb-91ce-
24c030599343&cKey=7d724368-46c7-47b8-8050-087713c49aef&mKey=6ffe1446-a164-476a-92e7-
c26446874d93
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=8092f9c1-a235-4394-80fa-
127f695cb77f&cKey=b6493065-dcbb-40e8-8e6b-1a89f4321202&mKey=6ffe1446-a164-476a-92e7-
c26446874d93
Clinical Cancer Research article: Adoptive Transfer of MART-1 T-
Cell Receptor Transgenic Lymphocytes and Dendritic Cell
Vaccination in Patients with Metastatic Melanoma
http://clincancerres.aacrjournals.org/content/20/9/2457.abstract
Anti-CD74 Abstract
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3404&sKey=1869083e-
dcfc-4125-a25f-0d5faf5b47be&cKey=706bae4d-b593-4f94-9c36-
80a3930c90c3&mKey=6ffe1446-a164-476a-92e7-c26446874d93
Ongoing research: find biomarkers to identify patients most likely
to respond to specific immunotherapies and exploring ways to
stimulate the immune system.

13. RepurposingRepurposing MetforminMetformin and Aspirin forand Aspirin for
Cancer Prevention and TreatmentCancer Prevention and Treatment
Epidemiologic and animal studies have associated metformin
and aspirin with a reduction risk of several cancers.
Retrospective analyses have correlated metformin with
increased survival in ovarian cancer.
Research is ongoing to understand how metformin and
aspirin may work to reduce risk and/or influence survival
Ongoing metformin clinical trials in ovarian cancer:
http://clinicaltrials.gov/show/NCT01579812;
http://clinicaltrials.gov/show/NCT02050009

14. Current Concepts in Organ Site ResearchCurrent Concepts in Organ Site Research
——A Systems Approach to Ovarian CancerA Systems Approach to Ovarian Cancer
Ronny Drapkin, Dana-Farber: Insights into the origins of ovarian cancer
◦ P53: earliest genetic mutation in HGS
◦ Telomere shortening, CNA (copy number alterations), HR dysfunction
(Homologous Recombination)
◦ Tumor Avatar Program
http://championsoncology.com/wp-content/uploads/2013/11/P.-Malaney-et-al-One-mouse-one-
patient-paradigm-New-avatars-of-personalized-cancer-therapy-Cancer-Lett-2013.pdf
◦ Mouse surgery study: FT no STC (serous tubal carcinoma), ovary had STC
(Theory: even if ovary is not origin, plays a role in seed and spread)
James Brenton, Cambridge: Detection of Circulating Tumor DNA (ctDNA)
and possible use as a biomarker for detection and monitoring treatment
(http://www.ncbi.nlm.nih.gov/pubmed/22649089)
Sandra Orsulic, Cedars-Sinai: Exploration in mice of the metabolic pathways
(Succinate Dehydrogenase) involved with ovarian cancer
Gordon Mills, MDAnderson: Study of potential targets: P13K, PTEN

15. Consortium efforts to discover ovarianConsortium efforts to discover ovarian
cancer risk variantscancer risk variants
Thomas Sellers, Moffitt
Genetic Associations and Mechanisms in Oncology
(GAME-ON): A Network of Consortia for Post-Genome
Wide Association (Post-GWA) Research
http://epi.grants.cancer.gov/gameon/
Follow-up of Ovarian Cancer Genetic Association and
Interaction Studies (FOCI)
Studying SNPs (single-nucleotide polymorphism) and
CNVs (copy number variations)
10% life-time risk for consideration of actionable
interventions

16. Interesting PostersInteresting Posters
Emiliano Cocco (Yale): Fluorescence imaging using Clostridium
Perfringens Enterotoxin carboxi terminal fragment (c-CPE) to
target metastatic chemotherapy-resistant human ovarian cancer
in xenograft mice
Luke Peppone (University of Rochester): The Effect of
YOCAS©® Yoga on Prescription Sleep Medication and OTC
Sleep Medication Usage in Cancer survivors with Impaired
Sleep Quality
Anees ChagPar (Yale): Physical activity is associated with
improved QoL in cancer survivors: A population-based analysis
Julia Parrish-Novak (Blace Bioscience): Tumor Paint™
technology detects naturally occurring solid tumors in dogs

17. Drug ResistanceDrug Resistance
Targeted therapies have produced dramatic regressions, but responses are
often short-lived because resistant cancer cells arise.
Researchers are studying mathematical theories and the mechanics of how
cancers evolve and develop resistance to treatments so strategies to
overcome resistance can be constructed.
Evolutionary dynamics of cancer in response to targeted therapy
(Martin Nowak, Harvard)
Researchers used a mathematical model describing the evolutionary dynamics
of lesions in response to treatment to study pancreatic, colorectal, and
melanoma cancer patients with metastatic disease. Dual therapy results in
long-term disease control for most patients, if there are no single mutations
that cause cross-resistance to both drugs.
SSP SIS Overcoming Drug Resistance (Charles Sawyers, MSKCC)
Effective strategies to overcome resistance are within reach, but widespread
sharing of genomic and clinical data is required to make progress. To gain
understanding, it is important that tumor samples are collected both before
and after treatments.

18. Drowning in Big DataDrowning in Big Data
The tools to uncover the genomic information
needed for personalized medicine have generated a
“data tsunami”
Velocity, Variety, Volume
Patient data expected to exceed 28 Petabytes (1
quadrillion bytes) by the end of 2014
Collaboration across institutions and disciplines is
needed to turn the massive amount of data into
usable information and knowledge to bring
effective personalized medicine to patients more
quickly
Data►Information►Knowledge/Evidence

19. What Is Research Advocacy?
Research advocacy brings a non-scientific viewpoint
to the research process and incorporates the
collective patient perspective into research, making
scientific and medical advances more timely and
effective for people with cancer.
A collective patient perspective is created when the
advocate has knowledge of others’ disease
experiences and conveys this collective patient
perspective rather than their singular experience.
Research advocates support well-designed studies
and help disseminate results that lead to new and
better methods to prevent, detect, and treat cancer.
NCI Office of Advocacy Relations

20. AACR Scientist↔Survivor Program
The AACR Scientist↔Survivor Program is designed
to build enduring partnerships among the leaders of
the scientific and cancer survivor and patient
advocacy communities worldwide.
The program exposes advocates to special lay-
language lectures, small group discussions and other
interactions that provide a solid background in cancer
research.
AACR Annual Meeting 2015: April 18-22,
Philadelphia, PA
http://www.aacr.org/home/survivors--
advocates/scientistharr;survivor-program.aspx

21. AACR Scientist↔Survivor Program
Before the meeting:
Submit application
Recommended reading
Poster
During the meeting:
Attend SSP sessions and general sessions
Present poster
Working group challenge question
Connect with researchers and advocates
After the meeting:
Disseminate information

22. AACR SSP Special Interest Sessions
Personalized Medicine
Advances in Immunotherapy
The Role of Big Data
Video: http://www.youtube.com/watch?v=_sZSWuRY3vk
The Biomechanics of Cancer
Night at the Lab, Peter Kuhn Laboratory at Scripps
◦ Circulating Tumor Cells (CTCs)
◦ Ovarian cancer being studied
Cancer Action Alliance
◦ URGENT: only 6-8% of grant submissions are funded
◦ Support NIH and hold accountable
◦ AACR Hill Days; Rally for Medical Research
◦ Sign up for alerts: AACR Cancer Action Alliance and Cancer Policy Monitor
(http://www.aacr.org/home/public--media/science-policy--government-
affairs/advocacy-tools/aacr-cancer-action-alliance.aspx)

23. AACR Scientist↔Survivor Program
SSP participants were encouraged to:
◦ Embrace the complexity of cancers
◦ Learn about the evolutionary dynamics of cancers
◦ Consider a systems approach to understanding and
treating cancers
Cancer is a complex adaptive system
◦ The Whole is more and different than the sum of the
parts
◦ Cancer occurs in context

24. AACR SSP Poster: 5x5 SurveyAACR SSP Poster: 5x5 Survey

25. Navigating Uncharted Waters: Exploring the
Resources Patients Use to Manage Long-Term
Recurrent Ovarian Cancer
METHODS: A 30-question online survey was offered to ovarian cancer survivors
who have had 5 or more lines of treatment or managed persistent or recurrent
disease for 5 or more years.
RESULTS: 25 respondents provided information about their experiences managing
ovarian cancer, including comfort level with participation in treatment decision-
making, amount of time spent discussing and researching new treatment options,
sources of information and clinical trial participation.
2+CLTR SUBGROUP:
◦ Most time researching options
◦ 5/6 BRCA+
◦ 3/6 Rely most on other survivors
CONCLUSIONS: Women managing persistent or recurrent ovarian cancer long-
term are comfortable participating in treatment selection, spend a great deal of time
researching their options and are using many resources to gain knowledge, including
each other and materials used by medical professionals. More research is needed to
improve outcomes and quality of life for all women diagnosed with ovarian cancer,
including those who are able to manage persistent or recurrent ovarian cancer long-
term.

26. Strategies for Dealing with ResearchStrategies for Dealing with Research
Information OverloadInformation Overload
Oxfordjournals.org

27. Treatment Decision-making: Consider the Options

28. Prioritizing Research: Consider More Than Headlines

29. Prevention vs. Risk ReductionPrevention vs. Risk Reduction
Understanding Absolute Risk Reduction Versus Relative Risk
Reduction (http://www.breastcancerdeadline2020.org)
◦ Let's say the risk of your cancer coming back is 4%. If you take
treatment X, the risk of your cancer coming back is 3%. The difference
between 4% and 3% is 1% (4% - 3% = 1%). The 1% decrease in risk is
called "absolute risk reduction."
◦ However, your doctor might talk about relative risk reduction instead.
He or she might say that your risk will be reduced by 25% if you take
treatment X. This is because 1% is 25% of 4% (1% - (3%/4%) = 25%).
The 25% decrease in risk is called "relative risk reduction."
◦ Ask your doctor to explain which kind of risk reduction she or he is
talking about. Sometimes the numbers can be very misleading.
What is the potential benefit?
What is the “cost” to achieve that potential benefit?

30. AACR Press Release, April 9, 2014:
Irregular Menstruation May Predict Increased Risk of Death
From Ovarian Cancer
http://www.aacr.org/home/public--media/aacr-press-releases.aspx?d=3325
Between 1959 and 1967, the Child Health and Development Studies enrolled more than
15,000 pregnant women and followed them for more than 50 years to study factors
impacting health during pregnancy. This report is based on 14,403 women who had a
single live birth. Cohn and colleagues used medical reports and self-reported data from
these women on their menstrual irregularity, including those whose cycles were longer
than 35 days, and those who had anovulation. The researchers used this information as a
proxy for polycystic ovarian syndrome (PCOS).
Findings:
◦ Those who had irregular menstrual cycles had a 2.4-fold increased risk of death due
to ovarian cancer.
◦ The incidence of late-stage ovarian cancer was twofold higher for women with
irregular or infrequent menstrual cycles, and this finding was consistent with their
higher risk for death from ovarian cancer.
◦ When the data were analyzed by ovarian cancer type, menstrual irregularities
increased risk for serous-type cancers and for endometrioid-type cancers by nearly
threefold and fourfold, respectively.

31. StrengthsStrengths
MedicalResearch.com
http://medicalresearch.com/cancer-_-oncology/ovarian-
cancer/irregular_menses_linked_to_higher_risk_ovarian_cancer/4856/
Irregular menses was defined by women’s own report of usual cycle length when
women were an average age of 26 years, during an in-person interview.
The study design was a prospective 50+ year follow-up of 14,403 pregnant
women recruited from 1959-1967 to the Child Health and Development Studies
(www.chdstudies.org). There were 103 incident cases and 65 ovarian cancer deaths
in this study.
We ruled out the contribution of infertility, the use of fertility drugs, or
the use of birth control bills as explanations of study findings. All women in this
study had a live birth, and medical records recorded pharmaceuticals prescribed 6
months prior to pregnancy.
Women with irregular menses constituted 13% of this large pregnancy cohort, and
so findings are relevant to many women. Given the lack of information about
risk factors, screening or biomarkers for ovarian cancer in young life, our findings
offer an opportunity for prevention and for understanding the 90% of ovarian
cancer cases that occur in women who do not have rare heritable germline
mutations or family history in a first degree relative.

32. WeaknessesWeaknesses
This study does not include infertile women (approx. 10% of all women). The
findings are not relevant to risk of ovarian cancer in infertile women.
There were some tumors with missing data on histology and stage, although there
was no evidence that missing data was correlated with irregular menses.
Other than serous tumors, the sample size for other tumor types was too small for
study. However, there was a suggestive finding that risk of death due to
endometrioid tumors was also elevated (p=0.14).
It is estimated that about 80% of women with irregular menses may have
polycystic ovarian syndrome (PCOS). However women without significant
symptoms (e.g. hirsutism, infertility, obesity) may never be diagnosed with PCOS.
Still we cannot determine with certainty whether it is predominantly
women with PCOS who were at increased risk of ovarian cancer in this
study.
Unexpected Findings:
◦ Contrary to the existing expectation that PCOS (characterized by less frequent
ovulation and irregular/long menstrual cycles) would protect the ovary. But
infrequent ovulation is not the only hallmark of PCOS, and there are a number
of anatomical, hormonal, and metabolic abnormalities associated with PCOS
that might explain the study findings.

33. What do we do with this information?What do we do with this information?
Research Advocate
RADAR: Unexpected finding--less frequent ovulation and irregular or long menstrual
cycles, expected to protect the ovary. What are anatomical, hormonal, and metabolic
abnormalities associated with PCOS that might explain the study findings?
Research Advocate
RADAR: Is there anything in this study that could yield clues about the etiology of ovarian
cancer, and provide opportunities for prevention, early detection for the 90% of ovarian
cancers that occur in women without evidence of heritable risk?
Previvor (or any woman without a cancer diagnosis)
ACTION: Record history of menstrual cycle and length (preferably during women’s early
reproductive years) and discuss with physician. Even though there are no known effective
screening strategies for early detection of ovarian cancer, results of clinical trials in
progress, or other advances could provide an opportunity to offer women with irregular
cycles screening options in the future.
Previvor (or any woman without a cancer diagnosis)
ACTION: Discuss personal risk and benefits of oral contraceptives with physician. There
is evidence that oral contraceptive use correlates with lower risk. Reminder: There is no
known effective screening strategy for ovarian cancer at this time.
Ovarian Cancer Survivor
NOT ACTIONABLE; DISCUSS with family members.

34. Resources
AACR Webcasts (some are free)
http://webcast.aacr.org/free?link=nav&linkc=my&utm_source=fb&utm_medium=wall&utm
_content=free&utm_campaign=2014am
Walter C. Willett: Diet and cancer: Status report in 2014
http://webcast.aacr.org/console/player/22788?mediaType=podiumVideo&
Article: http://acsh.org/2014/04/diet-cancer-little-evidence-direct-link/
2014 AACR Recaps from Cancer Today magazine
http://www.cancertodaymag.org/eventcoverage/Pages/toc.aspx?utm_source=twitter&utm
_medium=tweet&utm_content=cancertodaymag&utm_campaign=2014am
Cancer Today magazine
http://www.cancertodaymag.org
AACR Cancer Progress Report 2013
http://cancerprogressreport.org/2013/Documents/2013_AACR_CPR_FINAL.pdf
ASCO 2014 Ovarian Cancer Abstracts
http://abstracts.asco.org/144/CatAbstView_144_142_AT.html
Follow ASCO on Twitter: #ASCO14