Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves...

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Basic science seeks to understand how things work. In biology, this involves studying and explaining fundamental facts of life. By providing an understanding of how life works, basic biology research builds a foundation for applied science, which involves using this knowledge to affect change. Medicine is an example of an application of biology. Many advances in breast cancer research have stemmed from biological research. This timeline provides highlights. Why Study Biology? Basic Science: A foundation for application From bugs, to drugs, to breast cancer 1928 Penicillin: an accidental discovery revolutionizes medicine Jane Wei, BA, Thea Tlsty, PhD DNA engineering and the rise of biotechnology The yew tree and Taxol Duct Lobules hyperplasia atypical in situ invasive Normal Fleming discovered mold that could kill bacteria From the mold he isolated penicillin, the first antibiotic Began the antibiotic revolution Basic science and breast cancer today: personalizing treatments Using bacterial biology for biotechnology Restriction enzymes to cut DNA Bacterial gene transfer for genetic engineering Example: insulin producing bacteria Plant studies have revealed cancer-fighting compounds Paclitaxel (Taxol) was isolated from the bark of the Pacific yew tree This became an important chemotherapy drug Now, basic science continues to develop newer, less toxic versions of chemo drugs – such as Tesetaxel 1973 1993 Breast cancer treatments are increasingly being tailored to cancer biology By understanding why breast cancer progresses in some and not others, treatment can be individualized Acknowledgments: Thank you to Thea Tlsty and Laura Esserman for guidance. Progression of breast cancer (above) differs based on biological characteristics Bibliography: Worldwide Cancer Research National Breast Cancer Foundation Genome News Network National Cancer Institute Hereditary genetics Mutations are passed down BRCA genes and parp inhibitors Personalized medicine tests with more genes Tumor biology Changes in the tumor Estrogen receptors and Tamoxifen HER2 receptors and Trastuzumab Immune receptors and Pembro Tests such as Mammaprint and Oncotype that look at many genes

Transcript of Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves...

Page 1: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

Basic science seeks to understand how things work. In biology, this involves studying and explaining fundamental facts of life.

By providing an understanding of how life works, basic biology research builds a foundation for applied science, which involves using this knowledge to affect change.

Medicine is an example of an application of biology. Many advances in breast cancer research have stemmed from biological research. This timeline provides highlights.

Why Study Biology?

Basic Science: A foundation for application

From bugs, to drugs, to breast cancer

1928

Penicillin: an accidental discovery revolutionizes medicine

Jane Wei, BA, Thea Tlsty, PhD

DNA engineering and the rise of biotechnology

The yew tree and Taxol

Duct

Lobules

hyperplasia atypical in situ invasive Normal

• Fleming discovered mold that could kill bacteria

• From the mold he isolated penicillin, the first antibiotic

• Began the antibiotic revolution

Basic science and breast cancer today: personalizing treatments

• Using bacterial biology for biotechnology

• Restriction enzymes to cut DNA

• Bacterial gene transfer for genetic engineering

• Example: insulin producing bacteria

• Plant studies have revealed cancer-fighting compounds

• Paclitaxel (Taxol) was isolated from the bark of the Pacific yew tree

• This became an important chemotherapy drug

• Now, basic science continues to develop newer, less toxic versions of chemo drugs –such as Tesetaxel

1973

1993

• Breast cancer treatments are increasingly being tailored to cancer biology

• By understanding why breast cancer progresses in some and not others, treatment can be individualized

Acknowledgments: Thank you to Thea Tlsty and Laura

Esserman for guidance.

Progression of breast cancer (above) differs based on biological characteristics

Bibliography: Worldwide Cancer Research

National Breast Cancer FoundationGenome News Network

National Cancer Institute

Hereditary genetics • Mutations are passed down• BRCA genes and parp

inhibitors• Personalized medicine tests

with more genes

Tumor biology• Changes in the tumor• Estrogen receptors and Tamoxifen• HER2 receptors and Trastuzumab• Immune receptors and Pembro• Tests such as Mammaprint and

Oncotype that look at many genes

Page 2: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

How Do We Target and Treat Breast Cancer?

Yash Huilgol, Denise Wolf PhD

REFERENCES: 1. Nakai K, Hung M-C, Yamaguchi H. A perspective on anti-EGFR therapies targeting triple-negative breast cancer.American Journal of Cancer Research. 2016;6(8):1609-1623. 2. Dai X, Xiang L, Li T,

Bai Z. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes. Journal of Cancer. 2016;7(10):1281-1294. doi:10.7150/jca.13141. 3. Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation.

Cell. 2011; 144: 646-674. doi: 10.1016/j.cell.2011.02.013. 4. American Cancer Society. Targeted Therapy for Breast Cancer. 2017: https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-

cancer.html 5. Wolf D. Tea Time Talk: I-SPY 2. Lecture. Acknowledgements: Many thanks to Denise Wolf PhD, Laura Esserman MD MBA, and Brian Huang for their advice on this poster.

What are the Hallmarks of Cancer?

- The characteristics that make cancer cells

abnormal from regular cells (see Wheel below)

How scientists treat breast cancer?

- To stop breast cancer, drugs are used to disrupt

these abnormal behaviors.

How can modern modern biology improve

treatment?

- Scientists continue to find certain features in

a tumor or person’s biology that make

treatment more effective.

TARGETING THE HALLMARKS OF CANCER

Unfolded

Protein

Response

Inhibition

- Ganetespib

(HSP90i)

Anti-Proliferation Drugs for HER2+

cancer

- Trastuzimab (Herceptin)

- Pertuzumab (Perjeta)

Immunotherapy

Drugs

- Pembrolizumab

(Keytruda)

TIE 1/2

Inhibition

- AMG386

PARP Inhibition

- Targeting BRCA

1/2 for inherited

mutations

Scientists know

certain cancers

have certain

Hallmarks.

For example,

scientists know

that cancers avoid

the immune

system.

Some trials at

UCSF, like I-SPY 2

Trial, have built

upon advances in

personalized

medicine to bring

investigational

drugs like

Pembrolizumab by

targeting these

Hallmarks!

How have the Hallmarks of Cancer changed?

• Breast cancer-specific hallmarks are being refined as new

scientific discoveries are made!

So how do

scientists

identify the best

treatments?

One way is

biomarkers,

molecules or

enzymes, which

indicate to a

scientist that

someone has a

particular

targetable

cancer.

Breast Cancer

Types by

Biomarker:

- Triple negative

- HER2 receptor

positive

- Hormone

receptor+

(ER+/PGR+,

or HR+)

Page 3: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

Breast ImagingPoster Author: Jonah Donnenfield, UCSF Breast Care Center Intern

Poster Advisor: Nola Hylton, PhD

Mammography

Impact

Tomosynthesis

Ultrasound

MRI

1. Sissons, Clare. Breast Calcification. Digital image. Medical News Today. N.p., 7 June 2018. Web.

2. Breast Sonography. Digital image. Montgomery College, n.d. Web.

3. Nelson, HD. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009

U.S. Preventive Services Task Force Recommendation. Ann Intern Med. 164(4):244-55, 2016.

4. Seely, J.M., and T. Alhassan. “Screening for Breast Cancer in 2018—What Should We Be Doing Today?” Current

Oncology, 13 June 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC6001765/.

5. “Breast Cysts.” Www.Mayoclinic.org, Mayo Clinic, 19 June 2018, www.mayoclinic.org/diseases-conditions/breast-

cysts/diagnosis-treatment/drc-20370290.

6. O'Donnell, Chris. “Breast Cancer: MRI Findings.” Www.radiopaedia.org, 29 Jan. 2012,

radiopaedia.org/images/1677793.

(1)

10-15 minute procedure. Standard screening method for women.

Low-energy X-rays of the breast (~1/10 the radiation of a chest CT). Helps identify calcifications—the earliest signs of breast cancer.

3D mammography that combines multiple 2D mammograms into one navigable image. X-ray machine moves in an arc, taking snapshots from different perspectives. However, more data presents challenge for time efficient interpretation.

3D imaging minimizes tissue overlap that can result from traditional mammograms and helps find tumors

that normally go undetected.

15-30 minute procedure that usesharmless, high freq sound waves. Sound

echoes throughout tissue and reflects differently depending on composition. It’s a secondary screen while mammogram is a primary screen. Helps guide biopsies.

(2)

(6)

30-60 minute procedure. Magnetic field and harmless radioWaves generated by machine.

Machine listens backfor signals, whichchange based on tissuecomposition. Sees blood flow in ways that ultrasound and mammograms cannot.

Involves injection ofcontrast agent.

Women whoget screened have

lower risk of breastcancer death than those who do not.3

Thought to increase cancerdetection and lowersrate of false positives.4

Great diagnostichelper. Indicates ifmass is solid or fluid-filled (cystic).5

Capable ofidentifying cancers

that can’t be seenthrough other

imagingtechniques.

References

Calcifications/growths appear as white dots.

Traditionally, most women receive annual screens, but now there is personalized care. Check out:

Page 4: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

Breast Density & PreventionHolly Keane, MD and Hila Ghersin

Breast Density

What is it? What affects it? What does it have to do

with breast cancer?

Fatty Breast Dense Breast

On Mammogram:

Breast density describes the ratio

of fatty tissue to breast tissue

(fibrograndular tissue) on

mammograms.

Your breast density is NOT

determined by how your breasts

feel. But rather, by how they

appear on mammograms.

A variety of factors affect

breast density:

More about Age: For most women, breasts

become less dense with age.

However, in some women there is

little change over time.

More about Medications:

For postmenopausal

women, taking hormone

therapy (HT) may

increase breast density1.

Women with high breast density

are 4-5 times more likely to

develop breast cancer than

women with low breast density2. Scientists are still researching why

breast density increases risk.

Dense breast tissue makes it

harder for radiologists to see

cancer on mammograms. In California, the law states that women

have to be notified if they have high

mammographic breast density.

44% of women in the US have

dense breasts!3

1. Jack Cuzick, Jane Warwick, et al. Tamoxifen-Induced Reduction in Mammographic Density and Breast Cancer Risk Reduction: A Nested Case–Control Study, JNCI. 103(9): 744-752. 2. Boyd NF, Guo H, Martin LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 356(3):227-36, 2007. 3. Sprague BL, Gangnon RE, Burt V, et al. Prevalence of Mammographically Dense Breasts in the United States. JNCI: Journal of the National Cancer Institute. 2014;106(10). 4. Khan SA. Chapter 19: Management of Other High Risk Patients, in Harris JR, Lippman ME, Morrow M, Osborne CK. Diseases of the Breast, 5th edition, Lippincott Williams & Wilkins, 2014.

PreventionIn what ways are we

using breast density to

reduce cancer risk?Tamoxifen has been shown to reduce breast density.

When it reduces density, it is also thought to reduce the

risk of breast cancer4.

A trial at UCSF is looking at modifying breast cancer risk

by targeting breast density! Stay tuned for the results!

Talk to your doctor

about the ways breast

density affects your

cancer risk It’s important to remember that reducing breast cancer risk involves

targeting multiple potential risk factors. Breast density is just one piece

of the puzzle.

Page 5: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

Site Expansion

Insurance

Breast Health

Decisions ToolProvides high-risk women with

preventative strategies based on

their personalized risk score

3 main types of preventative

strategies that reduce risk:

Chemotherapy prevention

Risk-reducing surgery

Lifestyle modifications

Current participating sites

The first insurance provider to

support this study nationwide.

Ashley Gleaton, BA, Irene Acerbi, PhD, Laura Esserman, MD, MBA, Allison Stover-Fiscalini, MPH, Laura van ‘t Veer, PhD

Research reported in this poster was funded

through a Patient-Centered Outcomes

Research Institute (PCORI) Award (PCS-1402-

17049).

No

screening

until age 50

Biennial

MammogramAnnual

MammogramAnnual

Mammogram

+ MRI

Risk Model

Po

rta

l e

nro

llm

en

t a

nd

co

nse

nt

Athena

Health

Questionnaire

Mammogram

Genomic

profiling

Risk Factors:

Randomly AssignedThis helps Wisdom the most by

increasing scientific validity.

Self-SelectedYou choose which screening

group you are assigned to.

PersonalizedYour personal breast

cancer risk will

determine your

recommended

screening schedule.

Routine AnnualYou will receive a

routine annual

mammogram with the

same quality care we

are known for.

100,000 Women across America

How it Works

Future participating sites

How Does Personalized Screening Work?

Visit wisdomstudy.org for more information.

Eligibility Female

Age 40-74

No history of Breast

Cancer or DCIS

No history of

mastectomy in both

breasts

Enrollment criteria will

expand as the study

progresses!

Additional study sites

will open later in 2018.

JOIN NOW!With your help, we can find

answers. Share your

WISDOM.

wisdomstudy.org

Why WISDOM?Controversy over when

and how often to screen

for breast cancer.

We haven’t changed our

approach to screening in

30-40 years!

Can we personalize

screening based on

individual risk?

Fewer Side Effects

More acceptable

Promoting prevention

Page 6: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

Pembrolizumab and DCISPoster Author: Andre Dempsey, UCSF Breast Care Center Intern

Poster Advisor: Michael Campbell, PhD

What is Pembro?Pembrolizumab is a

drug that binds to

PD-1. This takes the

breaks off and revs

up the immune cells,

allowing them to

infiltrate and attack

the tumor.

Ductal Carcinoma In Situ

(DCIS)Despite the term “carcinoma” in its

name, DCIS is not cancer. By

definition, DCIS is non-invasive and

confined to the milk ducts of the

breast. However, DCIS is a risk factor

for the subsequent development of

invasive breast cancer. DCIS with a

higher risk of subsequent invasive

cancer is deemed “high risk DCIS”.

Cancer and the

Immune systemNormally, the immune system

recognizes foreign invaders

in the body (including

cancer) and destroys them.

Some cancer cells express a

protein, PD-1, which turns

off the immune cells’

response.

Pembro

Post-TreatmentPre-Treatment

T-cells

B-cells

Cancer cells

Clinical Trial: Treating High risk DCIS

with PembroHigh Risk DCIS seems to have abnormalities in the

immune response.

We are testing medicines like Pembro to see if we

can change the immune environment by injecting

pembro directly into the tumor.

Credit to www.breastcancer.org

Credit to the NIH National Cancer Institute

Credit to the NIH National Cancer Institute

Images courtesy of Michael Campbell

References1) Nakhlis, Faina, and Monica Morrow. "Ductal carcinoma in situ."

Surgical Clinics 83.4 (2003): 821-839.

2) Nanda, Rita, et al. "Pembrolizumab in patients with advanced

triple-negative breast cancer: phase Ib KEYNOTE-012 study." J

Clin Oncol 34.21 (2016): 2460-2467.

3) Pembrolizumab shows potential in breast cancer. (2015). Cancer

Discovery, 5(2), 100-101. doi:10.1158/2159-8290.CD-NB2014-184

Future TrialsSo far Pembro appears to be safe and can

increase T Cell counts. Our goal for the

next trial is to extend the number of

treatments to help get rid of DCIS.

Some immune

cells in the

tumor before

treatment

Many more

immune cells

after

treatment!

Page 7: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

Oncotype DX Test for Ductal Carcinoma in Situ (DCIS)Brian Huang, B.S.; Rita Mukhtar, MD

Lumpectomy

•Partial removal of breast

Mastectomy

•Full removal of breast

Active surveillance

• Monitoring without surgery

• (Being researched - currently a non-standard option)

Radiation Therapy

•Possibly given after a lumpectomy

Hormone Therapy

•Possibly given for certain tumor types

DCIS is the presence of abnormal cells in the milk duct/glands

of the breast

Some DCIS progress to

invasive cancer, and some do not

“In Situ” means it has not invaded outside the duct/gland1

This test looks at specific genes of a tumor and predicts how likely it is to return after a lumpectomy without radiation.

At UCSF, it helps determine recurrence risk with and without radiation.

That’s a lot of options! How do we decide?

Treatment for DCIS can be a mix and match between

two groups:

About one in every five breast tumors

diagnosed are DCIS2…

But not every case of DCIS is the

same!

A current study:

Does the score change how

patients/doctors approach DCIS?

Patients and providers are

surveyed to assess attitudes before

and after receiving oncotype results.

37 patients currently in this study at UCSF -

Stay tuned for further results!

References:1. “Brochures | Oncotype IQ®.” About the Oncotype DX Breast

Recurrence Score® | Oncotype IQ®, Genomic Health, 2016, www.oncotypeiq.com/en-US/resources/brochures.

2. Ernster, V L, et al. “Detection of Ductal Carcinoma in Situ in Women Undergoing Screening Mammography.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 16 Oct. 2002, www.ncbi.nlm.nih.gov/pubmed/12381707.

Contact InformationBrian Huang - [email protected]

If interested in joining the study:Jane Wei - [email protected]

Page 8: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

Invasive Lobular Carcinoma (ILC)Poster Author: Paul Kim (UCSF Breast Care Center Intern)

Poster Advisor: Rita Mukhtar MD, Ella F. Jones Ph.D.

References:1. http://www.mel

bournebreastcancersurgery.com.au/your-pathology-report.html

2. http://www.breastpathology.info/Common%20cancers.html

3. Perry, J. K., Lins, R. J., Lobie, P. E., & Mitchell, M. D. (2010). Clinical Science

4. https://lobularbreastcancer.org/resource-library/

5. Pestalozzi, B. C., Zahrieh, D., Mallon, E., Gusterson, B. A., Price, K. N., Gelber, R. D., … Goldhirsch, A. (2008). Journal of Clinical Oncology, 26(18), 3006–3014

6. http://www.radiologyassistant.nl/en/p47a585a7401a9/breast-mri.html#i4a18fafa42e20

7. http://mammibreastcare.com/what-is-mammi/

What is Invasive Lobular Cancer (ILC)?

• Originate from terminal duct lobular unit (TDLU)

• Invasive: Cancer cells have broken out of the lobule

• 2nd most common type of breast cancer (10-15%)

• Usually very strongly estrogen positive (ER+) (~90%)

• Grows in diffuse, linear pattern

• Lacks E-cadherin: Cells do not stick together

• Considered a slower growing cancer, and has a

tendency to recur later than IDC (ductal)

• Characteristics of diffuse tumors:

1. Harder to detect on Mammogram & MRI

2. Difficult to predict the extent of disease

3. Challenging surgical removal with clear margins

• Need a more reliable imaging tool

1. For an early detection of ILC

2. To measure ILC response to presurgical therapy

• There are studies looking to see if Mammi-PET is better

Why is ILC Unique?

What is the Advantage of Mammi-PET on ER+ ILC?

• Mammi-PET is a dedicated breast positron emission tomography (dbPET)

• To image ER+ breast cancers, we use a tracer, [F-18]fluoroestradiol (FES), similar to estrogen to target ER

• It may predict ILC response to pre-surgical hormone therapy & avoid the need for invasive tumor biopsies

• It may be complementary to MRI to characterize ER+ ILC

Assessment of ILC Response to Hormone Therapy with FES-dbPET

A B

• Mammi-PET is offered at UCSF!

• Please contact Ella Jones at [email protected] for

more information about Mammi-PET study at UCSF!

ILC

ILC

A: A 61 yo female

patient with grade 2

ILC in her right

breast. Dynamic

contrast-enhanced

(DCE)-MRI showed

contrast

enhancement

spanning 6.7 cm

DCE-MRI FES-dbPET

B: FES-dbPET showed

a max standard

uptake value

(SUVmax) at 15.83,

tumor-to-normal

ratio (TNR) at 4.81,

and total uptake

volume at 15.72 cm3

ILC

ILC

C

C: FES-dbPET after 2

months of Letrozole

showing a SUVmax

at 6.11, TNR at 2.54,

and total uptake

volume at 0.37 cm3

FES-dbPETD

D: DCE-MRI after 3

months of treatment

with Letrozole,

confirming the

favorable response

with no residual disease

DCE-MRI

BA

After 2 MonthsFrom Baseline

After 3 MonthsFrom Baseline

TDLU

Page 9: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

I-SPY 2An Innovative Trial for Newly Diagnosed Breast Cancer Patients

Investigations of Serial Studies toPredict Your Therapeutic Response

with Imaging And MoLecular Analysis

Laura Esserman, Don Berry, Julie Sudduth Klinger, Mark Magubana, Ruby Singhrao, Bin Chen, Lamorna Brown Swigart, Laura Van't Veer, Denise Wolf, Zelos Zhu, Andre Dempsey, Hope Rugo, Michelle Melisko, Mike Campbell, Nola Hylton, Christina Yau, Mi-Ok Kim, Smita Asare, Adam Asare, Amrita Basu, Karen DiGiorgio, Gill Hirst, Rosalyn Sayaman, Jenny Chen, Aheli Chattopadhyay, Jessica Gibbs, Melanie Hanson, Melanie Regan, Chiung-Yu Huang, Paul Kim, Angie DeMichele, Bev Parker, Barbara LeStage, Susie Brain, Fraser Symmans, Julia Wulfkule, Jeff Matthews, Andres Forero, Michael Ibara, Jane Perlmutter, Marie Davidian, Butch Tsiatis, Lajos Pusztai, Ann Barker, Doug Yee, Diane Heditsian, Atul Butte, Yiwei Shieh

Acknowledgments: Research supported by QuantumLeap Healthcare Collaborative, the Foundation for the National Institutes of Health , and a grant from the National Cancer Institute Center for Biomedical Informatics and Information Technology. Initial Support from the Safeway Foundation, the Bill Bowes Foundation, Quintiles Transitional, Johnson & Johnson, Genentech, Amgen, the San Francisco Foundation, Give Breast Cancer the Boot, Eli Lilly, Pfizer, Eisai, the Side Out Foundation, the Harlan Family, the Avon Foundation for Women, Alexandra Real Estate Equities, and private persons and families.

The I-SPY 2 TRIAL is a clinical trial for women with newly diagnosed, locally advanced breast cancer with a high risk of recurrence to test whether, before surgery, adding investigational drugs to standard chemotherapy leads to better outcomes than standard chemotherapy alone.

Looking to the Future: I-SPY 2+

NEW PATIENT

paclitaxel (control)

paclitaxel + Drug A*

AC Chemotherapy

doxorubicin + cyclophosphamide

SURGERY

MRIBlood DrawCore BiopsyMammaPrint

MRIBlood DrawCore Biopsy

MRIBlood Draw

MRIBlood DrawTissue

1 2 w e e k s 8 w e e k s

Features & Benefits of I-SPY 2

PERSONALIZEDINTERVENTION

SCREENING

DIAGNOSIS

TREATMENT

SURVIVORSHIP

ESCALATE

DE-ESCALATE REDUCEMORBIDITY

INCREASEEFFICACY

}}GOAL

RISK

RESPONSEor

RISK

RESPONSEor

paclitaxel + Drug B*

What is I-SPY 2?Aims of I-SPY 2+:• Assess residual cancer burden in patients at an earlier time point to

allow patients to switch to more efficacious treatments if necessary• Reduce toxicity without compromising efficacy• Maximize pCR rate for both individual patients and treatment regimes

*Active agents include: Pembrolizumab, Talazoparib, Patritumab, SGN-LIV1A

Page 10: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

THE MICROBIOME AND BREAST CANCERMadeline Matthys, Michael Campbell, PhD, Laura Esserman, MD

What is the human microbiome?

How BIG is the human microbiome?

Your brain is 3 lbs…

Your microbiome

is 3-6 lbs!

Tell me about the microbiome and BREAST CANCER!

Learn more by listening to a UCSF podcast from Hope Rugo, MD and Michael Campbell, PhD

• A collection of microorganisms (like bacteria) living in/on our bodies.

• Involved in upkeep of metabolism and immunity.

• Imbalance can lead to disease.

We have 3-10x more microbial cells than human cells in our body.

That’s 10-100 TRILLION microbes! (As a reference, there are ~250

billion stars in our galaxy.)

A UCSF study found multiple differences in the bacterial microbiome between healthy women, and women with breast cancer.• Women with breast cancer have more bacterioidus in gut (also linked to obesity!).• Women with breast cancer also have dysbiosis, or a less diverse gut microbiome

In the breast itself…• Healthy breast tissue has more lactobacillus and lactococcus compared to malignant tissue.• Malignant tissue also has more hyphomicrobium

So what does that mean for ME?• No evidence yet for how to change diet/supplementation.• But, studies show that intake of lactobacillus during breast feeding results in increased

lactobacillus in breast milk.1 So we know that bacteria can traffic from gut to breast tissue.• A diverse gut microbiome is better than non-diverse! You will likely want to intake many

strains of bacteria instead of just one if you consume probiotics or probiotic foods.

1 Rebeca Arroyo, Virginia Martín, Antonio Maldonado, Esther Jiménez, Leónides Fernández, Juan Miguel Rodríguez; Treatment of Infectious Mastitis during Lactation: Antibiotics versus Oral Administration of Lactobacilli Isolated from Breast Milk, Clinical Infectious Diseases, Volume 50, Issue 12, 15 June 2010, Pages 1551–1558, https://doi.org/10.1086/652763

Page 11: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

How to investigate the role of the immune system in controlling tumorsBy Kell Fahrner-Scott, Mike Campbell, PhD., Christina Yau, PhD.

T cellB cell

Mast cellTreg cell

Cell division markerTumor cell

Some cells of the immune system, including T cells, can fight cancer…

Many immune cells

How many immune cells are in the tumor?

How far away is each tumor cell

from the nearest T cell?

Few immune cells

Multiplex Assays: using fluorescence to mark cell types in microscope slides

Mast Cell

Neutrophils

Macrophages

Dendritic Cells

B-cells

NK CD56dim cells

NK cells

Cytoxic cells

Treg

Th1 cells

Exhausted T-cells

CD8 T-cells

T-cells

TILs

pCR

HR

Arm

CD274 (PD-L1)

PTPRCCD3DCD3ECD3GCD6SH2D1ATRAT1CD8ACD8BCD244EOMESLAG3PTGER4TBX21FOXP3CTSWGNLYGZMAGZMBGZMHKLRB1KLRD1KLRK1NKG7PRF1NCR1XCL1XCL2IL21RKIR3DL1KIR3DL2BLKCD19FCRL2KIAA0125MS4A1PNOCSPIBTCL1ATNFRSF17CCL13CD209HSD11B1CD163CD68CD84MS4A4ACEACAM3CSF3RFCARFCGR3BFPR1S100A12SIGLEC5CPA3HDCMS4A2TPSAB1

TILs

T-cells

CD8 T-cells

Th1 cells

Exhausted T-cells

Cytoxic cells

NK cells

Treg

NK CD56dim cells

B-cells

Dendritic Cells

Macrophages

Neutrophils

Mast Cell

Gene expression array: categorizing cells by the genes they express

Acknowledgments: Thank you to Yash Huilgol for organizing posters, and to Dr. Laura Esserman for advice and guidance.

Cell types present:

What methods can we use to study interactions between tumor and immune cells?

But sometimes, tumors keep these cells from getting into cancer tissue…

Close Medium Far

This method tells us about the location of cell

types in a tumor specimen.

Have many immune cells gotten into the tumor? Or has the tumor kept

them out?

A multiplex assay can only test for about 7 cell

types at once.

Different cell types express (“turn on”) different genes.

Look at these patterns

Estimate how many cells of each type are in a sample of tumor tissue.

Test for many types of immune cells!

This method doesn’t tell us about the exact location of each cell, like multiplex assays would.

These genes are markers of T cells, like the ones in the images above!

Rows represent genes, and color-coded clusters represent cell types!

Page 12: Why Study Biology?cancer.ucsf.edu/files/bcuiZ2/T4C_Intern_Posters_2018.pdfbiology, this involves studying and explaining fundamental facts of life. By providing an understanding of

PALLIATIVE CAREHarriet Rothschild, Mike Rabow, M.D.

• Not only for cancer patients• Not only for the elderly• Not only end-of-life care

• Not only hospice

Palliative care

End-of-Life care

Hospice

PALLIATIVE CARE IS...

Available in both the inpatient and outpatient settings (i.e. clinic,

home, telehealth)

Definition: clinical care from an interdisciplinary team focused on

improving patient’s symptoms and distress. It helps patients align their healthcare with their priorities and

values.

Provided concurrently with disease-directed treatments (e.g.

chemotherapy, surgery, and radiation)

Provided by a teamof doctors, nurses, social workers, chaplains, and other specialists

PROVEN TO...

Advanced Breast Cancer (ABC)

• 2 session workshop for patients and family members

• Complete an advanced healthcare directive

Be more effective when given early (>90 days before

end of life)

Prolong life (by 2.7 months in one study of people with lung cancer)

Reduce symptomburden, improve quality of care,

improve quality of life for patients &

families

Reduce costsof care

(typically by about $5,000 per patient)