The History of Oncology-Lessons Learned from Patients

enhanced by remarkable insights, science and prepared

minds

Lowell E. Schnipper, M.D.

Theodore W. and Evelyn G.

Berenson Distinguished Professor of

Medicine in the Field of Oncology

Harvard Medical School

Beth Israel Deaconess Medical Center

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Disclosures

Co-Editor-in-Chief, UpToDate,

OncologyCOPYRIGHT

Fifty Year Change in Cancer Death

Rates (CA journal Volume70, Issue1

January/February 2020)

Prevention-Primary

-Secondary

TreatmentCOPYRIGHT

The History of Oncology-Lessons Learned from

Patients

enhanced by remarkable insights, science and

prepared minds

Early history

Cancer biology and evolution of

therapies/chemoprevention

Infectious agents and cancer

Prevention

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History of Cancer

Edwin Smith Papyrus (1600BCE)

Hippocrates 460-370BCE

CA-4 bodily humors

Theodor Boveri 1862-1915

cancerous tumor begins

with a single cell in which

the makeup of its

chromosomes becomes

scrambled, causing the cells

to divide uncontrollably

Rudolf Virchow 1821-1902

All disease derives from

disordered cells, leukemia

“medicine is a social

science” and “the physician

is the natural attorney of the

poor.”

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History of Cancer

Surgeons-first cancer

specialists-poor outcomes

due to infectious

complications, insufficient

understanding of cancer

biology

1890’s: Halsted and the

radical mastectomy

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History of Cancer: Marie, Pierre and Irene Curie (Nobel Lauriates All)

Her achievements include the development of the theory of radioactivity (a term she coined),

techniques for isolating radioactive isotopes, and the discovery of two

elements, polonium and radium. Under her direction, the world's first studies were conducted

into the treatment of neoplasms using radioactive isotopes. (from Wikipedia)

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Epidemiology

Cancer Biology/

Pharmacology

Virology/Bacteriology

PreventionSurgical

Therapy

Getting from There to Here, and Beyond?

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Carole’s Story:Carole remembers what her sister’s mastectomy

looked like. Since having breast cancer 35 years

ago, she has had three bouts of reconstructive

surgeries. Her mother’s breasts were just

“butchered” during her 1972 surgery, says

Carole. At that time the motive was to remove the

cancer and little thought was put into how the

breasts would look postoperative.

Carol was surprised by how the diagnosis took

control of her physical and mental capacities.

“I was still in an emotional state,” she says. “Now that

I’ve been in it I understand girls going through it at

Michelle’s Place.” (where she volunteered)

Today it’s a different world for breast cancer patients.

Carole, who had Intraoperative Radiation Therapy, or

IORT, which delivers a concentrated dose of radiation

therapy to the tumor bed during surgery, explained

that you can barely even tell she had a lumpectomy

and radiation therapy.

BREAST CANCER

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Biology of Cancer – emphasis on clinical

biology (Fisher, 1968)

• There is no orderly pattern of tumor cell

dissemination.

• Regional lymph nodes are ineffective as

barriers to tumor cell spread.

• The blood stream is of considerable importance

in tumor dissemination.

• Operable breast cancer is a systemic disease.

• Variations in local-regional therapy are unlikely

to substantially affect survival.

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Support for the alternative hypothesis: survival outcome similar for mastectomy, lumpectomy and radiation, or lumpectomy alone.

Bernard Fisher Cancer Res 2008;68:10007-10020

©2008 by American Association for Cancer Research

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Epidemiology

Cancer Biology/

Pharmacology

Virology/Bacteriology

PreventionMedical

Therapy

Getting from There to Here, and Beyond?

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History of Cancer Chemotherapy

Vincent T. DeVita, Edward Chu

Cancer Research (2008) Volume 68, Issue 21

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\

By Unknown photographer - https://audiovis.nac.gov.pl/obraz/2360/, Public Domain,

https://commons.wikimedia.org/w/index.php?curid=79566637

From WW II to the War on Cancer:

Winternitz, Goodman and Gilman (Yale) Nitrogen Mustard and

Beginning of Lymphoma Therapy

Accidental exposure

BM suppression,

lymphopenia

Alopecia

Trial in lymphoma-prompt

regression (and re-

growth)COPYRIGHT

Fleming: chance and a prepared

mind

Tears, mucus,

and the launch of

the antibiotic eraCOPYRIGHT

History of Cancer ChemotherapyVincent T. DeVita, Edward Chu, Cancer Research (2008)

Volume 68, Issue 21

Brian Druker, M.D.

Discovery cis-

platinum Fischer, adjuvant therapy after br ca surgery

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Barnett Rosenberg, Ph.D.

discovered cisplatin, which led

to successful treatment for

testicular and other cancers.

Discovery of a Precious Metal: Chance and the Prepared Mind:

Platinum

1970: D.E. 27 y.o. man: widely met.

Testicular Ca to lungs, bones, liver-

succumbed after multiple courses

chemoRx

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The Dawn of Targeted anti-cancer therapy: Withdrawing Estrogen for the Treatment and Prevention of Breast

Cancer

George Thomas Beatson

Warneuke - [1], CC BY 4.0,

https://commons.wikimedia.org/w/index.php?curid=33202

460

In 1896 published a paper entitled On

Treatment of Inoperable Cases of

Carcinoma of the Mamma: Suggestions for

a New Method of Treatment, with

Illustrative Cases. This detailed his

pioneering treatment of three patients with

advanced breast cancer through

bilateral oophorectomyCOPYRIGHT

Tamoxifen: a ”wrong” outcome and an astute champion

Drs. Walpole Richardson Harper

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JNCI: Journal of the National Cancer Institute, Volume 90, Issue 18, 16 September 1998, Pages 1371–1388, https://doi.org/10.1093/jnci/90.18.1371

The content of this slide may be subject to copyright: please see the slide notes for details.

Tamoxifen and Chemoprevention

Cumulative rates of invasive and noninvasive breast

cancers occurring in participants receiving placebo or ...

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History of Cancer ChemotherapyVincent T. DeVita, Edward Chu, Cancer Research (2008)

Volume 68, Issue 21

Brian Druker, M.D.

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Mr. W and the accelerated phase of Chronic Myelocytic Leukemia (CML)

1971: Clinical Center NCI, NIH (I’m the clinical associate)

Mr. W. suffering from blast crisis of CML, many

unsuccessful treatments…

”Doc-you have to know when to let a man go”COPYRIGHT

How did the idea behind Gleevec

first come up?

• CML-rare

• Chronic then acute leukemia

• Ph1 chromosome (unique

oncogene)

• Nick Lydon and Brian Druker

CML: Huge Breakthrough

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Dawn of the Precision Medicine Age: STI571 (imatinib, Gleevec)

» Doug Jensen celebrated his 60th

anniversary with his wife last year. They

have six grandchildren and one great-

grandson.

» Mortensen married a physician who had

lost his first wife to breast cancer.

» Judy Orem now represents CML

patients in meetings with the Food and

Drug Administration. While Mortensen is

the longest living CML survivor, Orem is

the longest surviving patient

continuously on Gleevec.

» They had never met before the Gleevec

trials. They now consider themselves

best friends

NY TIMES: BOB TEDESCHIAPRIL 25, 2017

PHOTOS BY MEG ROUSSOS

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Hallmarks of Cancer: Implications for TherapyHanahan, Weinberg, Cell 2011

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Epidemiology

Cancer Biology/

Pharmacology

Virology/Bacteriology

Prevention Treatment

Getting from There to Here, and Beyond?

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Cancer Treatment

Unavailable to Most

² Cancer patients arrive

with advanced disease

uFew Rx options

uPrimary/secondary

prevention - of critical

importCOPYRIGHT

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George Papanicoloau

Romanian physician

Aurel Babeş made

similar discoveries in

the cytologic

diagnosis of cervical

cancer prior to Pap’s

publication, but the

latter did not

reference this,

hence, no Nobel

prize

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Cervical Cytology

»USPTF

Recommendations

for Screening with

Cytology

•Ages 21-65,

sexually active

•Every 3 years

•Every 5 years if

combined with HPV

DNA, begin age 30

» Annals Int Med (2012) 156:880

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Fig. 2 Age-standardised incidence of invasive cervical cancer and coverage of screening: England, 1971–1995. Reprinted with

permission from BMJ Publishing Group.

Henry C. Kitchener , Philip E. Castle , J. Thomas Cox

Chapter 7: Achievements and limitations of cervical cytology screening

Vaccine, Volume 24, Supplement 3, 2006, S63 - S70

http://dx.doi.org/10.1016/j.vaccine.2006.05.113

Impact of a Successful Cx CA Screening Program

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Pioneers in the Etiology of Cervical Cancer

Jackalope

Dr. Richard ShopeShope Papilloma Virus

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Harold Zur Hausen

Nobel Laureate, for

linking the Human

Papilloma virus to cervical cancer

Cx CA: young age, multiple

partners suggesting an. STD

Genital warts transformed to

Squamous cell CA (Bingo!)

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HPV as Etiologic Agent

President s Cancer Panel Annual Report 2012-2103

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Edward Jenner: the first vaccine

(cow or horse pox as inoculum?)

Early Chinese Smallpox

Vaccination

An HPV Vaccine:

Historical Precedent

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Prevention Cervical Cancer: HPV

Vaccine

L1 particles (immunogens) Doug Lowy and John Shiller

J Clin Invest. May 1, 2006; 116(5): 1167

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"I think it's fair to say that Barry prevented more cancer deaths

than any person who's ever lived.” (Jonathan Chernoff, on

Blumberg at his death).

In reference to Blumberg's discovery of the Hepatitis B

vaccine, former NASA administrator Daniel Goldin said, "Our

planet is an improved place as a result of Barry's few short

days in residence."

Preventing Liver Cancer

Hepatitis B Virus Vaccine

Baruch Blumberg 1925-

2001, Discovered Australia

Antigen (hepatitis B virus)

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Marshall and Warren: discovery of H. pylori

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Epidemiology

Cancer Biology/

Pharmacology

Virology/Bacteriology

Prevention Treatment

Getting from There to Here, and Beyond?

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Epidemiology:Pott, Percivall. [Chirurgical Observations] : Containing I. Observations Relative to the Cataract, Ii. Some Few Remarks, on

the Polypus of the Nose, Iii. Observations on the Cancer of the Scrotum, Iv. Observations and Cases Relative to the

Different Kinds of Ruptures, V. Observations on the Mortification of the Toes and Feet. Printed for Hawes, W. Clarke, and R. Collins ... 1775. Chirurgical Works of Percivall Pott, vol. 5.

Percival Potts:

• Surgeon, St.

Bartholomew's

• Pott’s Disease

• Early epidemiologist:

SCC scrotum-led to-Chimney Sweeper’s Act

-Benzopyrene (tobacco smoke)

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Richard Doll and Richard Peto: Pioneers

in Cancer Epidemiology

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Preventability of CancerColditz and Wei

Annu Rev Public Health. 2012

April ; 33: 137–156

15% of all cancers were

attributable to infectious agents

such as helicobacter pylori, human

papilloma virus (HPV), hepatitis B

and C, and Epstein-Barr virus.

Worldwide, tobacco use is the

single greatest avoidable risk

factor for cancer mortality and kills

approximately 6 million people

each year, from cancer and other

diseases.

WHO on Preventable CancerBetween 30-50% of all cancer cases

are preventable

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What the Future Will BringTreatments will emerge from

Biologic insights

\

Primary Prevention

-Global Commitment vs Tobacco & Obesity

Early Detection

--identification of specific

biomarkers,

e.g., ctDNA, proteins

--imaging advances to

localize primary site

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Rudolf Virchow (1821-1902): physician, biologist, anthropologist, social scientist

“medicine is a social science”

and “the physician is the

natural attorney of the poor”

“politics is nothing else but

medicine on a large scale”

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Ending Cancer: remarkable insights, understanding and prepared minds

Early history

-Virchow scientist, physician, social, scientist

Cancer biology and evolution of therapies

- Fisher: cancer as a systemic disease

-Goodman and Gilman: dawn of treating cancer with drugs

-Richardson and Walpole: targeted therapies, e.g., Tamoxifen, Imatinib

-

Infectious agents that cause cancer:

-Zur Hausen, HPV and Cervical Cancer

-Baruch Blumberg: Australia Antigen

-Warren and Marshall: H. pylori

Prevention:

-Potts

-Doll and Petot: tobacco

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What if we built cancer centers and nobody came?

“Let’s Make Cancer History” MDACC

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