Summer 2012 Newsletter - UCSF Helen Diller Family ...

Special Interest
Articles:
• Hormone receptor
negative breast
cancer: Improving the
effectiveness of
chemotherapy by
targeting immune
cells
Page 1, cont. Page 6
• 5 th International
Workshop on Breast
Densitometry and
Mammography-
Based Risk
Assessment
Page 2
• Views from an
advocate: Strategies
to stay sane – post
treatment
Pages 3
• Athena Breast Health
Network
Page 4
• Targeted Cancer
Therapy Enters
Phase I Clinical Trial
Page 5
• BOP members
participate in Tri-
Valley SOCKs Bras
for the Cause
Page 6
• Going West to do
some SPY-ing (article
from EBCC)
Page 7
• BCC Volunteer
Participates in
American Association
for Cancer Research
(AACR) Scientist
Survivor Program
(article from Breast
Cancer Connections)
Page 8
Editor: Karla
Kerlikowske, MD
Professor of
Medicine,
Epidemiology and
Biostatistics, UCSF
Bay Area Breast Cancer
SPORE Newsletter
Specialized Program of Research Excellence at the University of California San Francisco
Hormone receptor negative breast cancer: Improving the
effectiveness of chemotherapy by targeting immune cells
By Hope Rugo, MD, Shelley Hwang, MD, and Lisa Coussens, PhD
Triple-negative breast cancer (TNBC)
refers to a heterogeneous group of tumors
that are defined on the basis of absent
hormone receptors, estrogen (ER) and
progesterone (PR), as well as the HER-2
receptor and protein. TNBC are often
associated with worse outcome due to
aggressive tumor cell activity and fewer
options for effective treatment. Some of
these cancers are also associated with
inherited abnormalities in the BRCA
genes. In the advanced disease setting,
many of these tumors are fast-growing
with a short duration of treatment response
and rapid development of resistance to
standard therapy.
Breast cancer can be classified by patterns
of gene expression into several subtypes,
one of which is referred to as basal-like.
Most but not all TNBC are categorized as
basal-like, and basal-like or TNBC
accounts for ~15% of breast cancer
diagnoses. Compared to other breast
cancers, TNBC is commonly of higher
grade, occurs more frequently in younger
women and those of African American
descent, and is associated with an
increased probability of metastasis as well
as poorer survival. High treatment
responses are seen when patients with
TNBC are treated with primary
chemotherapy before surgery and many of
these women will be cured of their
disease, however relapses still occur and
are commonly seen within the first three
years after initial diagnosis. Approximately
20% of women diagnosed with early stage
breast cancer will develop systemic
recurrence and 5% will present at time of
initial diagnosis with spread of cancer to
other organs (metastatic disease). A
disproportionate percent of patients with
metastatic breast cancer will have TNBC.
For this group, although chemotherapy is a
critical component of treatment with
improved cancer related symptoms and
prolonged survival, all patients will
eventually succumb to their disease.
Improving treatment for TNBC is a critical
goal of breast cancer research.
While breast cancer has not historically
been linked to inflammation or infection, it
exhibits tumor-associated inflammation
characterized by infiltration of white blood
cells into developing and progressing
tumors. In breast cancers, macrophages
(a type of white blood cell) are the most
plentiful immune cell type present.
Recently, several investigators have
shown that tumor-associated
macrophages are independently increased
in TNBC. Supporting this finding, a
macrophage response gene expression
signature was identified in 17-25% of
breast cancers associated with low ER and
PR as well as significantly worse outcome.
PLX3397 is an oral agent that blocks
macrophages and has been shown to be
safe in humans with cancer. Compelling
animal data from the laboratory of Dr. Lisa
Coussens using a transgenic mouse
model of mammary carcinogenesis
demonstrated that treatment of late-stage
Continued on Page 6

Bay Area Breast Cancer SPORE Newsletter
The 5 th International Workshop on Breast Densitometry
and Mammography-Based Risk Assessment was held
June 9-10, 2011 in San Francisco, with 160 participants
representing more than 50 different institutions from
around the world. Investigators attending presented
research on new methods to measure breast density,
genetics and biology of breast density and use of breast
density in clinical practice to determine at what age to start
screening mammography and how often to be screened.
Breast density research is clinically relevant since it is one
of the strongest risk factors for breast cancer. Breast
density is a radiological term and that describes the
relative amounts of fat, epithelial, and connective tissues
that appear on a mammogram due to differences in X-ray
attenuation. Fat appears radiolucent or dark, while
epithelial and connective tissues are radiographically
dense and appear light or white (Figure 1). When
comparing women that have mostly white on their
mammogram (high breast density) to those that have
mostly dark (low breast density), women with high breast
Page 2
5 th International Workshop on Breast Densitometry and Mammography-Based
Risk Assessment
By Karla Kerlikowske, MD, UCSF Breast SPORE Investigator
density are at 4 to 6-fold higher risk of developing breast
cancer. For the purposes of this article, high breast density
is defined as an amount of greater than 50% dense tissue
seen on imaging. Of women undergoing mammography,
32% show high density, which exceeds the prevalence of
most risk factors such as family history of breast cancer.
Key findings presented at the 5 th International workshop
include:
• Volume of breast density measured as either
fibroglandular volume or percent fibroglandular volume is
strongly associated with breast cancer risk and improves
the accuracy of risk assessment over clinical risk factors
alone.
• For women aged 40 to 49 years with high breast density,
and with either a first-degree relative with breast cancer
or history of a prior breast biopsy, the benefits versus
harms for performing mammography every two years is
similar to screening an average-risk woman in her
fifties every two years.
• Women with fatty breasts have a decreased risk of
breast cancer. Women with high breast density have
decreased expression of CD36 that helps
development of fat cells in the breast.
• Women aged 50 to 59 years with low breast density
(fatty breasts) could be screened less often than
every two years.
• High breast density is strongly and positively
associated with breast cancer risk for several tumor
subtypes including estrogen-receptor (ER) positive
breast cancer, triple negative breast cancer and
HER2 positive breast cancer.
• rs10995190 single-nucleotide polymorphism (SNP), a
DNA sequence, is associated with breast cancer risk
and high breast density suggesting that the genetics
of breast cancer and breast density may be linked.
Figure 1: Left panel low
density and right panel high
breast density.
• BreastCare (Breast Cancer Risk Education) study is
evaluating a tablet-based intervention to increase
patient knowledge about her personal breast cancer
risk including factors that increase risk such as
breast density, and increase patient-physician
discussion of risk-reduction practices.
The workshop was chaired by Drs. Karla Kerlikowske,
John Shepherd and Steve Cummings and sponsored
by UCSF, Daniel and Phyllis Da Costa Funds of the
CPMC Foundation with contributions from the
California Breast Cancer Research Program,
American Cancer Society and the Matakina
International Limited. The next workshop will be held in
2013.

Bay Area Breast Cancer SPORE Newsletter
Page 3
Views from an Advocate: strategies to stay sane – post treatment
By Hannah Klein Connolly, Breast SPORE Advocate
As a UCSF research advocate, I am
often asked, “what do you do?” I was
initially unclear about my role. Sure, I
had done plenty of investigation on
the topic of breast cancer following
my own diagnosis. But, I wondered
what did I truly know about the
biology of cancer and the world of
research; how was I to make an
impact?
Armed with the desire to create
change, and an interest in science
(keep in mind, my last science class
was at least 30 years ago) and well
into my own treatment, I responded to
an inquiry on a bulletin board in the
UCSF Helen Diller Breast Cancer
Center.
I had worked in breast cancer
activism in the early 1990s and had
designed the original breast cancer
flag. Having worked with the pioneers
in the activist movement from Breast
Cancer Action and Breast Cancer
Fund, the choice to become a
research “advocate” felt natural and
empowering. I would have the
opportunity to speak on behalf of
breast cancer patients to those
studying and treating breast cancer.
Simply put, research advocates are
trained to advocate for the
advancement of treatment for
patients. Through advocacy, doctors
and scientists have the ability to hear
patients’ experiences and concerns.
The only barrier - my lack of scientific
knowledge!
Still undeterred, I began attending
weekly Wednesday morning Breast
Oncology Program (BOP) research
meetings. My mind would glaze over
after an hour of listening to scientists
pontificate about the ‘new downregulated
receptor…’. After these
meetings, I would speak with other
SPORE advocates in effort to gain an
understanding of these discussions. It
became very apparent to me that I
needed the basics. That was when I
learned about NBCC’s Project LEAD,
a weeklong, intensive science course
about breast cancer.
I was fortunate this summer to have
been accepted and to have taken part
in project LEAD. It was an amazing
experience. Incredible professors
from all over the country taught
classes from early morning into the
evening. We lived, breathed, and
bathed biology, statistics, and breast
cancer research. That amazing
week’s crash course enabled me to
go back to the BOP meetings and ask
meaningful questions amongst the
researchers.
Now as a trained advocate, speaking
on behalf of breast cancer patients, I
can truly help these scientists find
more efficient ways to collaborate and
communicate as they move research
from the laboratory to the clinic.
Along this extended breast cancer
journey, I have also had a variety
of speaking opportunities. I have
given presentations at the UCSF
Breast Oncology Program
Scientific Retreat in 2011, the
UCSF didactic course, Biology of
Breast Cancer offered through the
Department of Laboratory
Medicine, the 2011 Breast Cancer
SPORE External Advisory Board
on behalf of the Advocacy Core,
and the NCI site visit as a Patient
Advocate on the Bay Area
Physical Sciences and Oncology
Center.
What, you may ask, comes next? I
will be working with the Tissue
Utilization Committee helping to
determine how tissue samples are
to be used. I look forward to
addressing pertinent issues about
tissue use that are important within
the patient community – after all,
as a patient advocate, we are the
face of breast cancer to
researchers who have made it
their life work to solve these
complex questions!
The Bay Area Breast Cancer SPORE
Newsletter is produced annually by
the SPORE Advocacy and Tissue &
Outcomes Cores at UCSF.
It is mailed to all current study
participants as well as breast care
surgeons, oncologists, researchers,
and Breast Oncology Program
Members at UCSF, CPMC and
SFGH.
If you have questions or comments
about the material printed in this
newsletter, or if you would like to have
additional copies sent, please call the
Outcomes Office at:
(415) 353-9763.
More information about SPORE and
related studies, as well as archived
newsletter editions, is available at:
http://cancer.ucsf.edu/breast_spore

Bay Area Breast Cancer SPORE Newsletter
The Athena Breast Health Network
Alexandra Solomon, UCSF Athena Program Manager
The Athena Breast Health Network (Athena) is a unique
collaboration among the five University of California (UC)
medical/cancer centers (UCSF, UC Davis, UCLA, UC
Irvine, and UCSD), the Graduate School of Public Health
at UC Berkeley, and many other public and private
partners. Athena was founded by Dr. Laura Esserman
and is sponsored among others by the University of
California Office of the President and the Safeway
Foundation.
Athena is integrating clinical care and research in order to
revolutionize the delivery of breast care. By standardizing
the collection of data from both patients and physicians,
integrating molecular profiling of tumors at the time of
breast cancer diagnosis, and creating an unparalleled
biospecimen repository, Athena will enable personalized
care informed by science and will fuel continuous
improvement in treatment options and outcomes.
Key components of Athena include:
• Identifying women at high risk for breast cancer who will
be offered prevention services and decision support.
Page 4
• A comprehensive informatics strategy that includes
tools to collect, analyze and distribute clinical and
research data in real time.
• Web-based decision tools for patients and providers
to translate clinical information into treatment options
– allowing physicians to tailor treatment to biology,
patient preference and clinical performance.
• A data and biospecimen repository to support largescale,
longitudinal studies that will enable tailored
prevention and treatment strategies.
Underpinning these goals is a commitment by Athena
clinicians and researchers across California to share
data, as well as a culture that supports continuous
clinical improvement. With this unique collaboration,
Athena aims to change the choices for patients today
and create a better future for all women at risk of
developing breast cancer.
Athena started to enroll women who are coming to
UCSF for their mammography screening in December
2011 and will roll out in the clinic by summer of 2012.

Bay Area Breast Cancer SPORE Newsletter
Targeted Cancer Therapy Enters Phase I Clinical Trial
John Park, MD, UCSF Breast SPORE Investigator
Targeted therapies have been described by many as
the most promising new approach to cancer treatment,
but in many cases have shown disappointing potency
against cancer. In research initiated under the NCI
Breast Cancer SPORE Program, we have developed a
strategy that combines molecular targeting against
specific types of tumors and special drug delivery
capabilities that exemplifies a multifunctional
nanotechnology approach to cancer treatment (1). Our
Breast Cancer SPORE project involves a close
collaboration with the laboratories of Drs. James D.
Marks and Chris Benz as well as my lab. We have
developed novel, very small particles that contain
cancer drugs carried in the blood stream. These
particles are called nanoparticle/liposomal agents and
are directed to tumor cells via monoclonal antibody
(MAb) fragments. Realization of this strategy required
new antibody technologies for targeting the correct
tumor cells and an advanced delivery system that
could carry the drugs in the bloodstream to the tumor.
This technology has yielded HER2-targeted immuneliposomal
doxorubicin (HER2-targeted ILs-dox), as
well as other liposomal delivery systems containing
different MAbs and drugs.
These drug-containing immunoliposomes bind HER2overexpressing
(her-2-positive) tumors, and are then
taken up by the tumor cells to damage it. These anti-
HER2 immunoliposomes loaded with the
chemotherapy doxorubicin display potent and selective
anticancer activity against HER2-overexpressing
tumors since the drug is targeted to tumor cells that
overexpress HER2. This new delivery system has
superior efficacy over all other treatments tested,
including some of the most commonly-prescribed
chemotherapies (2). Our anti-HER2 immunoliposomal
doxorubicin agent is able to spare low-HER2
expressing non-cancer cells, including normal heart
cells (3); this may mean reduced cardiotoxicity as
compared to standard chemotherapy.
Page 5
Clinical trials
Working with the NCI Drug Development Group
(DDG), we developed a procedure for manufacturing
this new nanoparticle drug (4,5). We have also
collaborated with industry partners for the actual GMP
manufacturing, toxicology and clinical development;
the many steps involved in these collaborations were
long and arduous. Ultimately, the manufactured agent,
called MM-302, was observed to be safe in preclinical
studies, and the FDA granted an Investigational New
Drug (IND) application in 2010. The multicenter Phase
I clinical trial has now been initiated, and patients have
begun to receive this new treatment. Patients must
have HER2-positive advanced breast cancer
previously treated with trastuzumab (aka, Herceptin).
The trial has opened at Karmanos (Detroit, MI) and
UCSF. Dr. Pamela Munster, Director of the Early
Phase Clinical Trials program, leads the UCSF Phase
I portion.
Meanwhile, another agent developed within our
SPORE research, nanoliposomal CPT-11, has just
entered Phase III clinical trials for advanced pancreas
cancer.
The discovery of new and better cancer treatments is
an important enterprise. Academic centers, with their
strong basic research capabilities, must be
encouraged to further innovate from initial discoveries
of targets and technologies to fully translational clinical
products. Concerns about declining productivity in new
molecular entities and drug approvals from the
pharmaceutical industry highlight the importance of
“diversification” of the discovery process.
REFERENCES
1. Park, J.W. Nanotechnology in oncology. ASCO 2006
2. Park JW, Hong K, Kirpotin DB, Colbern G, Shalaby R, Baselga J, Shao Y, Nielsen
UB, Marks JD, Moore D, Papahadjopoulos D, and Benz CC. Anti-HER2
immunoliposomes: enhanced anticancer efficacy due to targeted delivery. Clin.
Cancer Res. 2002, 8:1172-1181.
3. Wickham, T. J. et al. Preclinical safety and activity of MM-302, a HER2-targeted
liposomal doxorubicin designed to have an improved safety and efficacy profile
over approved anthracyclines. Proc. SABCS, [Abstract P3-14-09] (2010).
4. Nellis DF, Ekstrom DL, Kirpotin DB, Zhu J, Andersson R, Broadt TL, Ouellette TF,
Perkins SC, Roach JM, Drummond DC, Hong K, Marks JD, Park JW, and Giardina
SL. Preclinical manufacture of an anti-HER2 scFv-PEG-DSPE, liposome-inserting
conjugate. 1. Gram-scale production and purification. Biotechnol. Progress 2005,
21 (1), 205 -220.
5. Nellis DF, Giardina SL, Janini G, Shenoy SR, Marks JD, Tsai R, Drummond DC,
Hong K, Park JW, Ouellette TF, Perkins SC, and Kirpotin DB. Preclinical
manufacture of an anti-HER2 scFv-PEG-DSPE, liposome-inserting conjugate. 2.
Conjugate micelle identity, purity, stability and potency analysis. Biotechnol.
Progress 2005, 21 (1), 221 -232.

Bay Area Breast Cancer SPORE Newsletter
Hormone Receptor Negative Breast Cancer, continued
tumor-bearing mice with PLX3397 in combination with
the chemotherapy drug paclitaxel (Taxol) reduced
macrophage infiltration as well as both primary tumor
growth and lung metastasis. Based on these exciting
findings, we hypothesized that blocking the function of
macrophages or eradicating their presence in tumor
tissue will improve outcome for women receiving
chemotherapy for metastatic disease. Our Komen
funded research includes 1) determining the efficacy of
decreasing macrophages in combination with
chemotherapy in mouse models of basal-like TNBC; 2)
Outcomes Office
1635 Divisadero Street
San Francisco, CA 94115
PHONE:
(415) 353-9763
FAX:
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EMAIL:
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Page 6
identifying the immune infiltrate associated with TNBC
versus other types of breast cancer to identify those
most likely to respond to macrophage-targeted therapy;
and 3) conducting a Phase Ib/II clinical trial testing a
new chemotherapy agent, eribulin, combined with
PLX3397, in women with metastatic TNBC. In addition,
we are starting a phase Ib clinical trial testing the safety
of PLX3397 in combination with paclitaxel (Taxol) in
patients with advanced cancer, and will then study this
combination in the multi-center novel neoadjuvant trial,
ISPY-2.
UCSF Breast Oncology Program (BOP) Participates in Tri-Valley SOCKs Bras for the
Cause Walk 2012
On Saturday, May 12 th the UCSF
SOCK BOPers walked a fun and
exhilarating 10-Kilometers (6.2
miles) at the Tri-Valley SOCK’s Bras
for the Cause walk. Walkers were
adorned in wildly decorated bras as
they made the 10-K trek in
Pleasanton. They were met by
applause the entire way from
hardworking volunteers, passersby,
and several cars decorated in bras;
one dutifully titled: the Sag Limo.
The walkers concluded by passing
through a path of candles lighting
the way to the final evening
festivities. Each light represented a
family member or friend who was
touched by breast cancer. Walkers
found the bags they had personally
commemorated and seeing that
their bag was one of many was an
extremely moving finish to a fun and
challenging walk.
The walk was organized by Tri-
Valley SOCK’s (Stepping Out for
Cancer Kures) an all volunteer
group who raises money for breast
cancer research, treatment, and
education. This 501(c)(3)
organization is a big supporter of
the Breast Oncology Program and
has made significant donations to
the development program.
BOP Walkers: Irene Acerbi and Juan Soto
Romano, Rosemary Akhurst, Dejana
Braithwaite, Lamorna Brown-Swigart, Jody
and Russell Frederickson, Nicole Flores,
Sarah Goins, Michelle Melisko, Miki Mori,
Carol Simmons, Malinda Walker and Andy
Chan, Denise Wolf, Sara Zheng.
BOP Volunteers: Diana Bretzinger, Diane
Heditsian, Alexandra Peck, Luika
Timmerman, Laura van ‘t Veer, Eunice Zhou

Bay Area Breast Cancer SPORE Newsletter
From European Breast Cancer Conference: The Bulletin March 23, 2012 article.
Featuring Laura van ‘t Veer, PhD, Bay Area Breast Cancer SPORE Principle Investigator
Page 7

Bay Area Breast Cancer SPORE Newsletter
From Breast Cancer Connections May 2012
Newsletter:
BCC Volunteer Participates in
American Association for
Cancer Research (ACCR)
Scientist ↔ Survivor Program
By Susie Brain
Page 8
At the American Association for Cancer Research Annual Meeting 2012: Cancer Advocates Poster Session. From left to
right: Jane Perlmutter, Ph.D., Lead Advocate, I-SPY-2 Clinical Trial; Susie Brain, poster presenter;, and Laura van't Veer,
Ph.D., Principal Investigator, Bay Area Breast Cancer SPORE, UCSF.
I recently had the opportunity to participate in the Scientist↔Survivor Program at the American Association
for Cancer Research (AACR) 103 rd Annual Meeting held in Chicago. The AACR’s Scientist↔Survivor Program
(SSP) was founded in 1999 by Anna D. Barker, Ph.D., formerly Deputy Director of the National Cancer
Institute and currently Director of Transformative Healthcare Networks at Arizona State University. She
envisioned a program “designed to build bridges and unity among leaders of the scientific community and
cancer survivors and advocacy communities worldwide.”
For an advocate like myself, participating in this program provided me with the opportunity to meet other
patient advocates and survivors, both from US and global cancer organizations, learn about state-of-the art
cancer research, and have the opportunity to interact with scientists and clinicians. The program also
included special lay-language lectures on key topics of interest and small group working sessions with
science mentors.
As SSP advocates, we also had the opportunity to attend many of the AACR meeting presentations including
forums, award lectures, plenary, and poster sessions – all listed in a program that was over 600 pages in
length! The exhibition hall featured over 400 exhibitor booths selling products ranging from specialized
laboratory pipettes, to environment enrichment toys for mice, to human cells and tissues. As a first-time
attendee, I was overwhelmed at the size of the event! Over 18,000 researchers from around the world
attend this five-day event – it was like arriving in a mini-city – with signposts to multiple meeting rooms,
lecture halls, snack bars, cafes, and even a souvenir shop! Our days were long, often beginning with 7:00
AM sessions and then ending with evening events such as the Annual Reception, President’s Reception, and
the Survivor-Advocate Dinner.
One of the requirements for SSP participation was to present a poster at the Cancer Advocates Poster
Session in the main exhibitor’s hall. For me this was a daunting project that I had to undertake prior to the
meeting. Luckily, I had the support of BCC and fellow advocates, and was able to present a professional 36”
X 48” poster titled “The Survivorship and Advocacy Task Force Model at Breast Cancer Connections”. I was
at my poster from 2:30 PM – 5:00 PM for one day, and was amazed how quickly the time went by as I
chatted with visiting scientists and advocates about its contents (see photo).
The take-home message from our collective group of 27 advocates is that we are all unified in our work to
find a cure for a particular cancer yet we need to support the emerging science that is looking at the
commonality of genomic pathways and mutations that underlie numerous cancers and not just the organ
site. We heard throughout the meeting that, in Churchill’s words, we are at the “end of the beginning” and
that there is a sense of optimism that amazing progress has been made in cancer research and with multidisciplinary
collaborations, including continued advocacy involvement, the future holds great promise.