This document provides information about breast cancer trends and facts. It discusses: - Breast cancer is the most common cancer in women and the second leading cause of cancer death in women. Incidence rates have been rising but mortality rates have been declining since 1989 due to earlier detection and improved treatments. - Risk factors include age, family history, dense breasts, obesity, hormone therapy use, alcohol consumption and lack of physical activity. Molecular subtypes have different survival rates and prevalence among racial groups. - Screening guidelines and risk assessment tools can help determine screening recommendations for average and high-risk women. Lifestyle changes like diet, exercise and weight management may lower risk. Targeted therapies have improved survival for HER2

1. Breast Cancer
2021

2. Some basic facts about breast cancer every
woman should know
- How common and at what age
- Are cases increasing or decreasing
- Is it clear what are the risk factors and can you
lower your risk
- How serious is it and are we making any
progress

3. Things that you can (easily?) do to lower your risk from breast
cancer
a.Make sure you get your mammogram
b.Try to avoid unwanted weight gain as you get older
c.Try to limit alcohol consumption
Hey, don’t look at me!

4. Trends in Breast Cancer Screening in a Safety-Net Hospital
During the COVID-19 Pandemic
AMA Netw Open. 2021;4(8):e2119929
number of cancer screening tests
received by women through CDC’s
National Breast Detection Program
(Early Detection Program) declined by
87% for breast cancer and during April
2020 as compared with the previous 5-
year averages for that month (Also
people gained weight and increased
alcohol consumption during the
pandemic)
https://www.cdc.gov/media/releases/
2021/p0630-cancer-screenings.html
COVID

5. UndesiredWeight Gain Since the Start of the Pandemic
women
Weight gain was
inversely related
to age
https://www.tfah.org/

6. Americans started drinking more as soon as the
pandemic began in full last year — a 54%
increase in national alcohol sales by March 21,
2020.
And as the pandemic wore on, so did Americans'
drinking.
A survey from late 2020 found 75% of Americans
increased their alcohol, women increased their
alcohol intake by 39% compared to 2019.
https://www.axios.com/americans-drinking-alcohol-
pandemic-29ee70d7-40ae-4e71-807a-3f4ad2ee19b8.html

7. “The only way to keep your health is
to eat what you don't want, drink
what you don't like, and do what
you'd rather not.”
MarkTwain
I’m not in the mood for any lectures right now!

8. By replacing your
morning coffee with
green tea…
You can lose up to 87%
of what little joy you
still have left in your
life.
There actually are some reliable data about the harm or benefits
of changing your behavior.

9. Most Common Cancer inWomen in 2021

10. 2nd Most Common Cancer Killer inWomen in 2021
Crude Death Rate
All: 289K/928 = 31%
Breast: 44K/282K = 15%
Lung: 62K/117K = 54%
Pancreas: 23K/28K = 82%

11. Most cancers are
sensitive to
hormone therapy
(estrogen receptor
positive) and are
negative for the
HER2 mutation
Breast Cancer Facts & Figures 2019-2020

12. Molecular Subtypes of breast Cancer
Name HR HER2 Surv/4y
Luminal A (73%) + - 92.5%
Luminal B (11%) + + 90.3%
HER2 enriched (4%) - + 82.7%
Triple Negative (12%) - - 77.0%
Howlader N, Cronin KA, Kurian AW, Andridge R. Cancer Epidemiol Biomarkers Prev. 2018 Jun; 27(6):619- 626.

13. New Invasive Breast Cancer by Age in
US for 2019
Some screening
guidelines limited to age
50 – 70y but note that
would cover only 51% of
the new cases of invasive
cancer

15. Incidence rates
highest in 70’s and
starts to fall back

16. Overall, up over the last 50 years

17. Trends in Incidence Rates of Invasive Breast Cancer in the
US , 1975 - 2016
Rise in older
women
Stable inYounger
women

18. Overall, flat over the last 20 years

19. Black rates now about the same as whites

20. Incidence rates are
highest inWhites but
Mortality highest in
Blacks (40% higher)
? Socioeconomic or
more aggressive
biology

21. Triple Negative much
more common in
Blacks (21%) than in
Whites (10%)
Some of the worse death
rate may be biology or
genetics

22. 64.3%
27.5% 5.8%

23. Slightly More advanced
stage distribution in
Black or Hispanic
Some of the higher death
rate may be due to
socioeconomic factors

24. The breast cancer mortality rate is 41% higher for Black women than
white women.
White women are almost five times more likely than Black women to
be referred for genetic counseling and testing Journal of
Clinical Oncology, Oct. 18, 2021
other research has found when testing was recommended by NCCN Black
patients less than 60%
white patients rate of 93%
Data also suggest Black patients are more comfortable working with providers of the
same race, but only about 3% of U.S. oncologists are Black.

25. Death rates have
been coming down
since the peak in
1989

26. https://seer.cancer.gov/explorer/
12.9%
2.5%

28. Cancer Median Age at Diagnosis Median Age at Death
All 66 (M) 65 (F) 72 (M) 73 (F)
Breast 63 (F) 69 (F)
Colon 67 (M) 70 (F) 70 (M) 75 (F)
Lung 70 (M) 71 (F) 71 (M) 73 (F)
Prostate 67 (W) 64 (B) 81 (W) 76 (B)
SEER Median Age of Cancer Patients at Diagnosisa,
2014-2018
By Primary Cancer Site, Race and Sex
https://seer.cancer.gov/csr/1975_2018/browse_csr.php?sectionSEL=1&pageSEL=sect_01_table.11
Median Age of Cancer Patients at Deatha,
2014-2018

29. Lose 9 people first 5 years
Lose 7 people next 5 years
Lose 4 people next 5 years

30. HER2 + no longer has a
significantly worse outcome
Triple negative the worste
outcome

31. Factor Comparison Numerical Risk
Gender Female: Male 100 X
Age 70y:30y 10 X
Dense Breast dense:normal 4.6 – 1.8X
Obesity postmen 2.85X
HRT progestin:no 1.26X
Alcohol per avg 1/day 1.07X
Breast Feeding per 12 mos or per kid 0.93X
Exercise nonactive 0.80X
Teen Pregnancy nullip or late pregn 0.50X
How Important are Risk Factors?

33. Increased almost twofold if a woman had
one affected first-degree relative
Increased threefold if she had two
affected first-degree relatives
threefold higher risk if the first-degree
relative was diagnosed before age 30
but the risk is only 1.5-fold higher if the
affected relative was diagnosed after age
60.

35. Balanced, Low-Fat Diet Reduces Risk of Death From Breast Cancer in
PostmenopausalWomen May 15, 2019
The federally fundedWomen’s Health Initiative (WHI) clinical trial of dietary modificationThis is the first large,
randomized clinical trial to show that diet can reduce the risk of dying from breast cancer.

39. Women's Health Initiative (WHI),
combined estrogen-progestin
replacement therapy was
associated with a significant
increase in invasive breast cancer
(HR 1.24)
menopausal hormone therapy and breast cancer

40. The risk of
breast cancer is
highest among
long term users
of hormone
replacement

43. https://www.cancer.gov/news-events/cancer-currents-blog/2020/breast-cancer-survival-exercise
met the minimum physical activity guidelines both before diagnosis and at the
2-year follow-up (after treatment) had a 55% reduced chance of their cancer
returning and a 68% reduced chance of death from any cause (not just breast
cancer)
did not meet the guidelines before diagnosis but met them at the 2-year follow-
up, the chance of recurrence or death was reduced by 46% and 43%,
respectively
For Women with Breast
Cancer, Regular Exercise
May Improve Survival
collected information on the physical activity levels of
women with high-risk breast cancer

44. bcrisktool.cancer.gov/calculator.html
The Gail Model

45. If the 5-year risk is
over 1.7%
consider taking
hormonal
medication to
lower the risk
Tamoxifen, Raloxifene
(Evista) or Aromatase
Inhibitors (Arimidex,
Aromasin, Femara)

47. Chances among 10,000 women who undergo annual screening mammography for 10 years: (A) of experiencing a
false-positive mammogram, undergoing a breast biopsy, and developing breast cancer;

48. Chances among 10,000 women who undergo annual screening mammography for 10 years of being cured of
breast cancer regardless of screening and averting death from breast cancer because of screening
mammography.
Is it worth
it?

50. For women of normal risk recommend annual mammograms at
age 40 with no upper age limit.
There is limited data on benefits from women > 70y since the trials
did not include them, however observational studies and computer
models show benefit out to age 80 – 84.
Mortality benefit in the trials was delayed for 5 to 7 years, so life
expectancy shorter than that may consider stop screening

51. Life Expectancy in Women
Current Age inYears

53. DifferentAdvice for High-RiskWomen

56. www.invitae.com/en

57. Cancer Without
Chemotherapy: ‘A Totally
Different World’
nytimes.com/2021/09/27/health/breast-cancer-chemotherapy-lung.html
The breast cancer treatment guidelines issued by the
NCI 30 years ago: chemotherapy for about 95 percent
of patients with breast cancer.
women 60 yo or older 35 percent of older women received
chemotherapy in 2012. That number fell to 19 percent by the end of
2019.
There are now at least 14 new targeted breast cancer drugs on the
market — three were approved just last year — with dozens more in
clinical trials and hundreds in initial development.

58. Changing Survival with Metastatic Breast
Cancer usingTargeted Drugs (not
chemotherapy)
Biomarker Survival Survival Now
90’s H/70’s E
HER2 + 20 Months 57 Months
ERP + 24 Months 64 Months

60. HER2 Positive Breast Cancer from the worst to
the best)
By 1987 it was known that if the breast cancer over
expressed HER2 (about 25% of women did) the prognosis
was much worse (median survival only 3 years compared
to 6-7 years)
First ever mono-clonal therapy (Herceptin) cancer for 1991
phase 1 trial, phase 3 1995 also get FDA approval for hercep
test by 1998 approved for metastatic and adjuvant in 2005
(standing ovation)

61. Human Epidermal Growth Factor Receptors on the surface of a cell
HER 2 malfunctions in about 25% of breast cancer cases

62. HER2 or human epidermal growth factor receptor
(EGFR) family
Amplification = too many copies of the gene
Overexpression = too many copies of the HER2 receptor
Instead of 20,000 receptors on the surface the cancer cell has 2 million

63. The Oncogene HER2
It is not inherited (germline) it is due to a
mutation that occurs after birth (somatic
mutation)

64. The growth
factor proteins
on the surface
of the breast
cancer cell

65. They combine and
start sending
signals to the
nucleus for the cell
to grow and divide

66. A healthy cell has
only 2 copies of
the gene, if too
many copies or a
mutation then
creates too many
copies and too
much growth

67. Too many growth
receptors on the
surface of the cell and
sending too may
signals for the cell to
grow and divide

68. Too much growth and cell
division leading to the
formation of a cancerous
tumor

69. TargetedTherapy for HER2 + Breast Cancer
Herceptin
Perjeta
Margenza
Lapatinib
Neratinib
Tucatinib
T-DM1
Enhertu

70. Antibodies
come in an
interfere with
the growth
factors

71. Antibodies also attract
immune cells that come in
an attack the cancer cell

72. HER2 inhibitors are
small molecules that
work inside the cell to
block the growth
receptors from sending
signals to the nucleus

73. The conjugates attach
chemotherapy
molecules to the
antibodies to sneak
them into the cancer
cell

74. Once it gets inside the cell the
chemotherapy molecules are
released killing the cell

75. Margetuximab –cmkb (Margenza)
Tucatinib (TUKYSA)
Now 8 Drugs toTreat Her2 + Breast Cancer

76. Herceptin
first ever
mono-clonal
antibodies
used to treat
cancer

77. Herceptin Perjeta

79. PERJETA and Herceptin target cells with too
much HER2
Combining Herceptin and Perjeta in HRER2 + cancers is even
more effective in treating this cancer

80. TDM-1

82. Also a conjugate using a monoclonal antibody to deliver
chemotherapy only to the cancer cells

83. Too many growth receptors on the surface of the breast cancer cell in HER2 + Cancer

84. The excessive number of growth receptors on the surface combine and start releasing growth signalling
into the cell

86. Tukysa works on the HER2 protein from inside the cell WhileTrastuzumab works on the extracellular part
Tucatinib a HER2 Inhibitor

87. A monoclonal antibody but they engineered the Fc portion to bind
even better to NK cells and get an immunotherapy boost to the
effectiveness

89. Cleveland Clinic StartsVaccineTrial againstTNBC
(Triple Negative Breast Cancer)
vaccine targets the milk protein α-lactalbumin and found that 70% to 80% of TNBCs produce too much α-lactalbumin.

90. NCCN.org

92. Patient Guidelines from the NCCN

93. Patient Animations from the NCCN

94. PatientWebinars from the NCCN

95. Breast Cancer
2021
https://sites.google.com/view/robert
-miller/home
Or
tinyurl.com/robertmillermd