The Cancer Chronicles (36 page)

52.
mitogenesis increases mutagenesis:
Ames and Gold, “Chemical Carcinogenesis.”

53.
Toxicologists defended the tests:
P. J. Infante, “Prevention Versus Chemophobia: A Defence of Rodent Carcinogenicity Tests,”
Lancet
337, no. 8740 (March 1991): 538–40; [
http://www.lancet.com/journals/lancet/article/PII0140-6736(91)91310-Q/fulltext
] P. F. Infante, “Use of Rodent Carcinogenicity Test
Results for Determining Potential Cancer Risk to Humans,”
Environmental Health Perspectives
101, suppl. 5 (December 1993): 143–48 [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519448
]; and I. Bernard Weinstein, “Cell Proliferation: Concluding Remarks,”
Environmental Health Perspectives
101, suppl. 5 (December 1993): 159–61. [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519446
]

54.
diverting attention from a genuine problem:
See, for example, Clapp and Jacobs, “Environmental and Occupational Causes of Cancer”; Devra Lee Davis and Joel Schwartz, “Trends in Cancer Mortality: U.S. White Males and Females, 1968–83,”
Lancet
331 (March 1988): 633–36 [
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(88)91426-2/abstract
]; and Devra Davis,
The Secret History of the War on Cancer
(New York: Basic Books, 2007).

55.
recent report by a White House advisory group:
Reducing Environmental Cancer Risk: What We Can Do Now,
2008–2009 Annual Report (Washington, DC: National Cancer Institute, April 2010). [
http://deainfo.nci.nih.gov/advisory/pcp/annualreports/pcp08-09rpt/PCP_Report_08-09_508.pdf
]

56.
The alternative would be to administer:
Reducing Environmental Cancer Risk,
11.

57.
“has been grossly underestimated”:
Reducing Environmental Cancer Risk, introductory letter, unpaginated.

58.
many scientists criticized the report:
David C. Holzman, “President’s Cancer Panel Stirs Up Environmental Health Community,”
Journal of the National Cancer Institute
102, no. 15 (August 4, 2010): 1106–13. [
http://jnci.oxfordjournals.org/content/early/2010/07/28/jnci.djq297.extract
]

59.
The National Academy of Sciences has described:
“Toxicity Testing in the 21st Century: A Vision and a Strategy (Washington, DC: National Academies Press, 2007). These ideas are beginning to be embodied in the Environmental Protection Agency’s Computational Toxicology Research program. [
http://epa.gov/ncct
]

60.
death rates from cancer did rise gradually:
Ahmedin Jemal et al., “Annual Report to the Nation on the Status of Cancer,
1975–2009, Featuring the Burden and Trends in Human Papillomavirus (HPV)–Associated Cancers and HPV Vaccination Coverage Levels,”
Journal of the National Cancer Institute
(January 7, 2013). See table 2. A summary with a link to the full report is available on the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) website. [
http://seer.cancer.gov/report_to_nation
]

61.
began decreasing modestly:
Adjusted for age, overall cancer mortality was about 199 people per 100,000 in 1975. Ten years later it was 211. By 2009, the latest year for which statistics have been tabulated, it had dropped to 173. See N. Howlader et al., eds., “SEER Cancer Statistics Review,” 1975–2009 (Vintage 2009 Populations), National Cancer Institute, Bethesda, MD, based on November 2011 SEER data submission, posted to the SEER website, 2012. [
http://seer.cancer.gov/csr/1975_2009_pops09
] The mortality details are in table 2.6 and incidence details in table 2.5. [
http://seer.cancer.gov/csr/1975_2009_pops09/browse_csr.php
]

62.
Incidence rates tell a similar story:
The 2012 report, cited earlier, doesn’t break down the rates so finely. I used table 1 of an earlier annual report: Brenda K. Edwards et al., “Annual Report to the Nation on the Status of Cancer, 1975–2006, Featuring Colorectal Cancer Trends and Impact of Interventions,”
Cancer
116, no. 3 (2010): 544–73. [
http://onlinelibrary.wiley.com/doi/10.1002/cncr.24760/full
]

63.
lack of exercise and excess weight are far more to blame
: The American Association for Cancer Research progress report for 2012 attributes 33 percent of cancer to tobacco, 20 percent to excess weight and obesity, 5 percent to lack of exercise, and just 5 percent to diet (figure 9, page 9). The report is on the AACR’s Cancer Progress website. [
http://cancerprogressreport.org
] The source of the AACR’s numbers is Graham A. Colditz, Kathleen Y. Wolin, and Sarah Gehlert. “Applying What We Know to Accelerate Cancer Prevention,”
Science Translational Medicine
4, no. 127 (March 28, 2012): 127rv4. [
http://stm.sciencemag.org/content/4/127/127rv4.abstract?sid=55e7c705-12c3-4aa9-bffb-c7fa7756a739
]

64.
A twenty-five-year retrospective
: Graham A. Colditz, Thomas A. Sellers, and Edward Trapido, “Epidemiology—Identifying the Causes and Preventability of Cancer?”
Nature Reviews Cancer
6, no. 1 (January 2006): 75–83. [
http://www.ncbi.nlm.nih.gov/pubmed/16372016
]

65.
found comparable numbers:
“Attributable Causes of Cancer in France in the year 2000,” International Agency for Research on Cancer website. [
http://www.iarc.fr/en/publications/pdfs-online/wrk/wrk3/index.php
]

66.
neighborhood cancer clusters:
K. J. Rothman, “A Sobering Start for the Cluster Busters’ Conference,”
American Journal of Epidemiology
132, no. 1 suppl. (July 1990): S6–13 [
http://aje.oxfordjournals.org/content/132/supp1/6.full.pdf+html
]; and Raymond Richard Neutra, “Counterpoint from a Cluster Buster,”
American Journal of Epidemiology
132, no. 1 (July 1, 1990): 1–8. [
http://aje.oxfordjournals.org/content/132/1/1.full.pdf
] Also see Atul Gawande, “The Cancer Cluster Myth,”
New Yorker,
February 8, 1999. For an evocative account of a cancer cluster investigation and the lessons learned, see Dan Fagin,
Toms River: A Story of Science, Folly and Redemption
(New York: Random House, 2013).

67.
even occupational clusters are uncommon:
For an assessment see P. A. Schulte et al., “Investigation of Occupational Cancer Clusters: Theory and Practice,”
American Journal of Public Health
77, no. 1 (January 1987): 52–56. [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1646814
]

68.
the same patterns are appearing:
Ahmedin Jemal et al., “Global Cancer Statistics,”
CA: A Cancer Journal for Clinicians
61, no. 2 (2011): 69–90; [
http://onlinelibrary.wiley.com/doi/10.3322/caac.20107/abstract
] P. Boyle and B. Levin, eds.,
World Cancer Report 2008
(Lyon: International Agency for Research on Cancer, 2008); [
http://www.iarc.fr/en/publications/pdfs-online/wcr/2008
] and World Cancer Research Fund/American Institute for Cancer Research,
Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective
(Washington, DC: AICR, 2007). Also see D. Max Parkin et al., “Global Cancer Statistics, 2002,”
CA: A Cancer Journal for Clinicians
55, no. 2 (February 24, 2009): 74–108. [
http://onlinelibrary.wiley.com/doi/10.3322/canjclin.55.2.74/abstract
]

69.
reverse smoking:
J. J. Pindborg et al., “Reverse Smoking in Andhra Pradesh, India: A Study of Palatal Lesions Among 10,169 Villagers,”
British Journal of Cancer
25, no. 1 (March 1971): 10–20. [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2008558
]

70.
unpacking the most recent SEER statistics:
Howlader et al., eds., “SEER Cancer Statistics Review.” For the highlights see Jemal et al., “Annual Report to the Nation.” I also referred to an earlier report, Betsy A. Kohler et al., “Annual
Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System,”
Journal of the National Cancer Institute
103, no. 9 (May 4, 2011), 1–23. [
http://www.ncbi.nlm.nih.gov/pubmed/21454908
]

71.
a decline or leveling off:
Jemal et al., “Annual Report to the Nation.”

72.
12.1 cases per 100,000, compared with 62.6:
Howlader et al., eds., “SEER Cancer Statistics Review,” table 1.4.

73.
Childhood cancers are among the very rarest:
Howlader et al., eds., “SEER Cancer Statistics Review,” table 28.1.

74.
Death rates … have fallen to about half:
Howlader et al., eds., “SEER Cancer Statistics Review,” table 1.2.

75.
the numbers jump all over the place:
Howlader et al., eds., “SEER Cancer Statistics Review,” table 28.2. The figures are for children age fourteen and under. Also see Trevor Butterworth, “Is Childhood Cancer Becoming More Common?” May 28, 2010, Research at Statistical Assessment Service (STATS) website, George Mason University. [
http://stats.org/stories/2010/childhood_cancer_may28_10.html
]

76.
Every cancer tells a different story:
For summaries, see Jemal et al. and the American Cancer Society’s annual reports, “Cancer Facts & Figures,” on the group’s website.

77.
What may appear to be a climb:
Martha S. Linet et al., “Cancer Surveillance Series: Recent Trends in Childhood Cancer Incidence and Mortality in the United States,”
Journal of the National Cancer Institute
91, no. 12 (June 16, 1999): 1051–58. [
http://jnci.oxfordjournals.org/content/91/12/1051.abstract
] Also see “Childhood Cancers,” National Cancer Institute website, reviewed January 10, 2008 [
http://www.cancer.gov/cancertopics/factsheet/Sites-Types/childhood
]; and Butterworth, “Is Childhood Cancer Becoming More Common?”

78.
prostate, lung, colorectal … are all higher:
Howlader et al., eds., “SEER Cancer Statistics Review,” tables 1.5 and 1.6.

79.
less cancer than blacks or whites:
Howlader et al., eds., “SEER Cancer Statistics Review,” table 2.5.

80.
the incidence of brain cancer:
Howlader et al., eds., “SEER Cancer Statistics Review,” table 3.16.

81.
For liver cancer Hawaii tops out:
Howlader et al., eds., “SEER Cancer Statistics Review,” table 14.16.

82.
“Nature and nurture affect the probability”:
Doll and Peto, “Causes of Cancer,” 1204.

1.
Among the chemicals:
National Toxicology Program,
Report on Carcinogens,
12th ed. (Research Triangle Park, NC: U.S. Department of Health and Human Services, 2011). [
http://ntp-server.niehs.nih.gov/?objectid=03C9AF75-E1BF-FF40-DBA9EC0928DF8B15
]

2.
First synthesized in 1844:
Michele Peyrone, “Ueber Die Einwirkung Des Ammoniaks Auf Platinchlorür,”
Justus Liebigs Annalen Der Chemie
51, no. 1 (January 27, 2006): 1–29. [
http://onlinelibrary.wiley.com/doi/10.1002/jlac.18440510102/abstract
] For a short biography of the discoverer, see George B. Kauffman et al., “Michele Peyrone (1813–1883), Discoverer of Cisplatin,”
Platinum Metals Review
54, no. 4 (Oct 2010): 250–56. [
http://www.platinummetalsreview.com/article/54/4/250-256
]

3.
how cells behaved in the presence of electricity:
Barnett Rosenberg, Loretta Van Camp, and Thomas Krigas, “Inhibition of Cell Division in
Escherichia coli
by Electrolysis Products from a Platinum Electrode,”
Nature
205, no. 4972 (February 13, 1965): 698–99. [
http://www.nature.com/nature/journal/v205/n4972/abs/205698a0.html
] Also see Gregory A. Petsko, “A Christmas Carol,”
Genome Biology
3, no. 1 (2002) [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC150444
]; and Rebecca A. Alderden, Matthew D. Hall, and Trevor W. Hambley, “The Discovery and Development of Cisplatin,”
Journal of Chemical Education
83 (2006): 728. [
http://pubs.acs.org/doi/abs/10.1021/ed083p728
]

4.
“God, you don’t often find things like that”:
“Interview with Barnett Rosenberg,” Sesquicentennial Oral History Project contributor, available online at Michigan State University Archives and Historical Collections, February 2, 2001. [
http://onthebanks.msu.edu/sohp/Object/2-D-E9/barnett-rosenberg
]

5.
Rosenberg went on to test the molecule’s effects:
Barnett Rosenberg, Loretta Vancamp, et al., “Platinum Compounds: A New Class of Potent Antitumour Agents,”
Nature
222, no. 5191 (April 26, 1969): 385–86. [
http://www.nature.com/nature/journal/v222/n5191/abs/222385a0.html
]

6.
scientists discovered how that works:
See, for example, Huifang Huang et al., “Solution Structure of a Cisplatin-Induced DNA Interstrand Cross-Link,”
Science
270, no. 5243 (December 15, 1995): 1842–45. [
http://www.sciencemag.org/content/270/5243/1842.abstract
] For a review of chemotherapy drugs and crosslinking, see Andrew J. Deans and Stephen C. West, “DNA Interstrand Crosslink Repair and Cancer,”
Nature Reviews Cancer
11, no. 7 (July 2011): 467–80 [
http://www.nature.com/nrc/journal/v11/n7/abs/nrc3088.html
]; and Laurence H. Hurley, “DNA and Its Associated Processes as Targets for Cancer Therapy,”
Nature Reviews Cancer
2, no. 3 (March 2002): 188–200. [
http://www.nature.com/nrc/journal/v2/n3/full/nrc749.html
]

7.
the penicillin of cancer:
Stephen Trzaska, “Cisplatin,”
Chemical and Engineering News
83, no. 25 (2005): 3. [
http://pubs.acs.org/cen/coverstory/83/8325/8325cisplatin.html
]

8.
sickening side effects:
“Cisplatin,” American Cancer Society website, last revised January 14, 2010. [
http://www.cancer.org/Treatment/TreatmentsandSideEffects/GuidetoCancerDrugs/CISPLATIN
]

9.
Doxorubicin has its own curious tale:
Klaus Mross, Ulrich Massing, and Felix Kratz, “DNA-Intercalators—The Anthracyclines,” in H. M. Pinedo and Carolien Smorenburg, eds.,
Drugs Affecting Growth of Tumours
(Basel, Boston: Birkhäuser Verlag, 2006), 19. [
http://books.google.com/books?id=iM6t34xl7wQC
]

10.
push down your white blood cell count:
“Doxorubicin,” American Cancer Society website, last revised November 7, 2011. [
http://www.cancer.org/Treatment/TreatmentsandSideEffects/GuidetoCancerDrugs/doxorubicin
]

11.
reports that the risk increases:
Giorgio Minotti et al., “Paclitaxel and Docetaxel Enhance the Metabolism of Doxorubicin to Toxic Species in Human Myocardium,”
Clinical Cancer Research
7, no. 6 (June 1, 2001): 1511–15. [
http://clincancerres.aacrjournals.org/content/7/6/1511.abstract
]

12.
Paclitaxel (or Taxol) was originally isolated:
Frank Stephenson, “A Tale
of Taxol,”
Research in Review,
Fall 2002, available online at the Florida State University Office of Research website. [
http://www.rinr.fsu.edu/fall2002/taxol.html
]

13.
The first chemo agents:
Alfred Gilman and Frederick S. Philips, “The Biological Actions and Therapeutic Applications of the B-Chloroethyl Amines and Sulfides,”
Science
103, no. 2675 (April 5, 1946): 409–36. [
http://www.sciencemag.org/content/103/2675/409.extract
] For more about the story, see Vincent T. DeVita and Edward Chu, “A History of Cancer Chemotherapy,”
Cancer Research
68, no. 21 (November 1, 2008): 8643–53 [
http://cancerres.aacrjournals.org/content/68/21/8643.abstract
]; and Bruce A. Chabner and Thomas G. Roberts. “Chemotherapy and the War on Cancer,”
Nature Reviews Cancer
5, no. 1 (January 1, 2005): 65–72. [
http://www.nature.com/nrc/journal/v5/n1/abs/nrc1529.html
]

14.
covered under the 1993 Chemical Weapons Convention:
Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on Their Destruction
(New York: Organisation for the Prohibition of Chemical Weapons, 2005). Available on the OPCW website. [
http://www.opcw.org/chemical-weapons-convention
]

15.
“UPSC has a propensity”:
Alessandro D. Santin et al., “Trastuzumab Treatment in Patients with Advanced or Recurrent Endometrial Carcinoma Overexpressing HER2/neu,”
International Journal of Gynecology & Obstetrics
102 (August 2008): 128–31. [
http://www.ncbi.nlm.nih.gov/pubmed/18555254
]

16.
a cancer of older, thinner women:
David M. Boruta II et al., “Management of Women with Uterine Papillary Serous Cancer,”
Gynecologic Oncology
115 (2009): 142–53 [
http://www.ncbi.nlm.nih.gov/pubmed/19592079
]; Amanda Nickles Fader et al., “An Updated Clinicopathologic Study of Early-stage Uterine Papillary Serous Carcinoma (UPSC),”
Gynecologic Oncology
115, no. 2 (November 2009): 244–48 [
http://www.medscape.org/viewarticle/711270
]; C. A. Hamilton et al., “Uterine Papillary Serous and Clear Cell Carcinomas Predict for Poorer Survival Compared to Grade 3 Endometrioid Corpus Cancers,”
British Journal of Cancer
94, no. 5 (March 13, 2006): 642–46; [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361201
] Sunni Hosemann, “Early Uterine Papillary Serous Carcinoma: Treatment Options Tailored to Patient and Disease Characteristics,”
OncoLog
50, nos. 4–5 (April–May 2010): 4-6; [
http://www2.mdanderson.org/depts/oncolog/articles/10/4-5-aprmay/4-5-10-compass.html
] and Carsten Gründker, Andreas R. Günthert, and Günter Emons, “Hormonal Heterogeneity of Endometrial Cancer,” in Lev M. Berstein and Richard J. Santen, eds.,
Innovative Endocrinology of Cancer,
vol. 630 of
Advances in Experimental Medicine and Biology
(New York, NY: Springer, 2008), 166–88. [
http://www.springerlink.com/content/r086275l87307hj4
]

17.
“There are no risk factors”:
Felice Lackman and Peter Craighead, “Therapeutic Dilemmas in the Management of Uterine Papillary Serous Carcinoma,”
Current Treatment Options in Oncology
4, no. 2 (2003): 99–104.

18.
as few as 5 to 10 percent:
Boruta et al., “Management of Women with Uterine Papillary Serous Cancer.” Also see Brij M. Sood et al., “Patterns of Failure After the Multimodality Treatment of Uterine Papillary Serous Carcinoma,”
International Journal of Radiation Oncology, Biology, Physics
57, no. 1 (September 1, 2003): 208–16 [
http://www.ncbi.nlm.nih.gov/pubmed/12909235
]; and Hadassah Goldberg et al., “Outcome After Combined Modality Treatment for Uterine Papillary Serous Carcinoma: A Study
by the Rare Cancer Network,”
Gynecologic Oncology
108, no. 2 (February 2008): 298–305. [
https://www.ncbi.nlm.nih.gov/pubmed/18096209
]
[email protected]

19.
I found an essay:
S. J. Gould, “The Median Isn’t the Message,”
Discover
6 (June 1985): 40–42. [
http://cancerguide.org/median_not_msg.html
]

20.
“All evolutionary biologists know”:
Gould, “The Median Isn’t the Message.”

21.
Should she be getting topotecan?:
Robert W. Holloway, “Treatment Options for Endometrial Cancer: Experience with Topotecan,” part 2,
Gynecologic Oncology
90, no. 3 (September 2003): S28–33. [
http://www.ncbi.nlm.nih.gov/pubmed/13129493
]

22.
He attached abstracts from three papers:
Holly H. Gallion et al., “Randomized Phase III Trial of Standard Timed Doxorubicin Plus Cisplatin Versus Circadian Timed Doxorubicin Plus Cisplatin in Stage III and IV or Recurrent Endometrial Carcinoma,”
Journal of Clinical Oncology
21, no. 20 (October 15, 2003): 3808–13; [
http://www.ncbi.nlm.nih.gov/pubmed/14551299
] David Scott Miller et al., “A Phase II Trial of Topotecan in Patients with Advanced, Persistent, or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study,”
Gynecologic Oncology
87, no. 3 (December 2002): 247–51; [
http://www.ncbi.nlm.nih.gov/pubmed/12468321
] and Scott Wadler et al., “Topotecan Is an Active Agent in the First-line Treatment of Metastatic or Recurrent Endometrial Carcinoma,”
Journal of Clinical Oncology
21, no. 11 (June 1, 2003): 2110–14. [
http://www.ncbi.nlm.nih.gov/pubmed/12775736
]

23.
Nancy’s oncologist gave us a paper:
Alessandro D. Santin, “HER2/neu Overexpression: Has the Achilles’ Heel of Uterine Serous Papillary Carcinoma Been Exposed?”
Gynecologic Oncology
88, no. 3 (March 2003): 263–65. [
http://www.ncbi.nlm.nih.gov/pubmed/12648572
]

24.
receptors that respond to human epidermal growth factors:
The mechanism is a little more convoluted than is often described. See “Targeted Therapies for Breast Cancer Tutorial: Inhibition of HER2,” National Cancer Institute website. [
http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies/breastcancer_htmlcourse/page3
]

25.
It is usually just called
HER2:
The awkward name came about after two laboratories discovered the gene independently (in humans and in rats): Alan L. Schechter, Robert A. Weinberg, et al., “The Neu Oncogene: An erb-B-related Gene Encoding a 185,000-Mr Tumour Antigen,”
Nature
312, no. 5994 (December 6, 1984): 513–16 [
http://www.nature.com/nature/journal/v312/n5994/abs/312513a0.html
]; and A. Ullrich et al., “Human Epidermal Growth Factor Receptor cDNA Sequence and Aberrant Expression of the Amplified Gene in A431 Epidermoid Carcinoma Cells,”
Nature
309, no. 5967 (June 31, 1984): 418–25. [
http://www.nature.com/nature/journal/v309/n5967/abs/309418a0.html
]

26.
A drug called Herceptin:
The story of its development is told in Robert Bazell,
Her-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer
(New York: Random House, 1998).

27.
His name had been mentioned in an episode of
The West Wing
:
Lawrence K. Altman, MD, “Very Real Questions for Fictional President,” Doctor’s World,
New York Times,
October 9, 2001. [
http://www.nytimes.com/2001/10/09/health/the-doctor-s-world-very-real-questions-for-fictional-president.html
]