1. BREAST, PROSTATE AND TESTICULAR CANCER: AN OVERVIEW
Cynthia L. Martel, M.D., Ph.D.
USC Oncology
Pasadena
March 12, 2012

2. BREAST, PROSTATE AND TESTICULAR CANCER - TOPICS FOR DISCUSSION
Incidence rates
Risk factors
Prevention
Treatment

3. CANCER – A DEFINITION
Uncontrolled progressive growth of tissue which invades other organs, destroying the substance of the organs, and/or spreads (metastasizes) to other parts of the body
Any part of the body can become cancerous
Approximately half of all men and one third of all women will be diagnosed with cancer during their lifetimes

4. SOME ADDITIONAL DEFINITIONS
Screening
Testing asymptomatic individuals to determine if they have a disease
Chemotherapy
Strictly defined, refers to any medication used to treat a disease, but as commonly used, refers to drugs which kill cancer cells by damaging the machinery that allows the cell to divide

5. SOME ADDITIONAL DEFINITIONS
Radiation therapy
Use of high energy beams, generally directed at the patient from a large machine outside of the body, to kill cancer cells
Unlike chemotherapy, which circulates throughout the body, radiation is a local treatment which only affects the part of the body at which the beam is aimed

6. BREAST CANCER – THE SCOPE OF THE PROBLEM
Breast cancer is the most common cancer in American women, other than non-melanoma skin cancer.
The lifetime risk of getting breast cancer for a woman in the U.S. is about 1 in 8

7. BREAST CANCER – THE SCOPE OF THE PROBLEM
Breast cancer causes more deaths among American women than any other cancer except for lung cancer
Approximately 200,000 women (and approximately 2000 men) are diagnosed with breast cancer in the U.S. each year, and about 40,000 women die of breast cancer each year

8. BREAST CANCER – THE SCOPE OF THE PROBLEM
For unclear reasons, the incidence of breast cancer steadily increased in the 1980’s and 1990’s
The incidence of breast cancer decreased in 2003, possibly due to a decline in the use of hormone replacement therapy (HRT)

9. BREAST CANCER – THE SCOPE OF THE PROBLEM
The risk of dying of breast cancer has been steadily decreasing since the 1990’s
The survival rate for breast cancer varies greatly depending upon how advanced the cancer is at diagnosis
Approximately 20% of all women with breast cancer will die of the disease

10. BREAST CANCER – WHAT PUTS YOU AT RISK?
Gender
Breast cancer is extremely rare in men
Age
Breast cancer is very rare in women younger than 40, but the risk steadily increases with age into the 70’s, and then decreases slightly
Prior history of cancer in the opposite breast

11. BREAST CANCER – WHAT PUTS YOU AT RISK?
Family history of breast cancer, especially among first degree relatives (mother, sister, daughter)
Families with a strong history of breast cancer, especially at a young age (less than 50) should consider testing for hereditary mutations which predispose to breast cancer

12. BREAST CANCER – WHAT PUTS YOU AT RISK?
History of certain breast disorders
Atypical hyperplasia
Lobular carcinoma in situ (LCIS)
Radiation to the chest (e.g. as treatment for another type of cancer)

13. BREAST CANCER – WHAT PUTS YOU AT RISK?
Weight
Weight gain and being overweight may slightly increase the risk of breast cancer in postmenopausal women
Dietary factors
High intake of animal fat may increase risk*
*JNCI 2003, 95:

14. BREAST CANCER – WHAT PUTS YOU AT RISK?
Alcohol intake
Smoking
Data on whether smoking increases the risk of breast cancer are conflicting, but some data suggest that smoking modestly increases breast cancer risk
Physical inactivity
*JNCI 2003, 95:

15. BREAST CANCER PREVENTION
For women at average risk
The only intervention that can be recommended is lifestyle modification (maintain a healthy weight, limit alcohol intake etc.)
For women at increased risk
Drugs which block the action of estrogen, such as tamoxifen and raloxifene, can decrease the risk of hormone sensitive breast cancers
Prophylactic mastectomy

16. BREAST CANCER DIAGNOSIS
In the U.S., the majority of breast cancers are detected not because of any symptom, but by screening (primarily mammography)

17. BREAST CANCER DIAGNOSIS
Most breast cancers not discovered through screening are discovered because the women notices a breast mass
Other symptoms usually do not occur until the cancer is far advanced, and vary depending upon the part of the body affected

18. BREAST CANCER SCREENING
Breast self-examination
Breast examination by a health care provider
Mammography

19. BREAST EXAMINATION Breast self examination
No longer routinely recommended
Studies have failed to prove that it is beneficial

20. BREAST EXAMINATION Breast examination by a health care provider
Every 1-3 years for women age 20-39
Every year for women 40 and older
The above is per the recommendations of the American Cancer Society

21. MAMMOGRAPHY
It has been shown that undergoing regular mammograms decrease a woman’s risk of dying of breast cancer
Historically, there was general agreement that women should have a mammogram every year starting at age 40

22. MAMMOGRAPHY
In 2009, the U.S. Preventive Services Task Force (USPSTF) generated a huge controversy by recommending against regular mammograms for women in their 40s, and advised that women age have a mammogram every 2 years
Why the change?

23. MAMMOGRAPHY
When the USPSTF made their 2009 recommendations, there was relatively little new data on the usefulness of mammography in younger women
The data that were available did not change our understanding of the effectiveness of mammography

24. MAMMOGRAPHY
The change in recommendations was based on a calculation of the number of women age who have to be screened with mammography to prevent one death from breast cancer – 1904
This number was felt to be too high to justify the potential harms of mammography, such as unnecessary biopsies

25. BREAST CANCER TREATMENT
Surgery
Radiation
Medical therapies
Chemotherapy
Hormonal therapy
Herceptin

26. BREAST CANCER TREATMENT - SURGERY
Removal of the breast tumor
Total mastectomy, which can be followed by breast reconstruction if the woman desires it
Breast conserving surgery (“lumpectomy”)
For most women, either mastectomy or breast conserving surgery is reasonable, and will lead to equivalent odds of survival

27. BREAST CANCER TREATMENT - SURGERY
Sampling of the lymph nodes that drain the breast, which are in the axilla (armpit), to rule out spread of the cancer

28. BREAST CANCER TREATMENT - RADIATION
Mandatory after lumpectomy in almost all patients
May be recommended even after mastectomy in women with large tumors or involvement of multiple lymph nodes by cancer
Generally well tolerated, but occasionally causes severe scarring of the skin and second cancers in the area treated with radiation

29. BREAST CANCER TREATMENT - CHEMOTHERAPY
Depending upon the regimen used and the characteristics of the tumor, chemotherapy decreases the risk of recurrence by ~30-40% on average
This is a relative risk reduction

30. BREAST CANCER TREATMENT - CHEMOTHERAPY
Due to the potential for serious side effects, chemotherapy is not generally recommended for patients who are at very low risk for recurrence of their cancer

31. BREAST CANCER TREATMENT – HORMONAL THERAPY
Approximately 60-70% of all breast cancers are hormone sensitive (i.e. fueled by estrogen)
Hormonal therapy refers to medication which decreases estrogen levels or prevents estrogen from stimulating the cancer cell
Examples include tamoxifen and Arimidex
Decreases relapse rate by ~40% (relative reduction)
Low risk of serious side effects, so used for most patients with hormone sensitive tumors

32. BREAST CANCER TREATMENT – HERCEPTIN
Approximately 20% of breast cancers have increased expression of the HER-2/neu protein (“HER-2 positive”)
The use of Herceptin, an antibody against the HER-2/neu protein, decreases the risk of relapse of HER-2 positive breast cancer by nearly 50% (relative reduction)
Rarely causes allergic reactions and congestive heart failure
$$$$$$

33. BREAST CANCER TREATMENT – LIFESTYLE MODIFICATION
Reduction of dietary fat intake has been shown in one study to reduce the risk of breast cancer recurrence by 2.6% (absolute reduction)
The goal was to decrease fat intake to 15% of caloric intake
The benefit was seen primarily in women with hormone insensitive breast cancer
Chlebowski et al., JNCI 2006, v. 98, 1767

34. BREAST CANCER TREATMENT – LIFESTYLE MODIFICATION
Another study with a similar design failed to demonstrate that a low fat diet prevented breast cancer recurrence
Pierce et al., JAMA 2007, v. 298, 289

35. PROSTATE CANCER – THE SCOPE OF THE PROBLEM
Prostate cancer is the most common cancer in American men, excluding non-melanoma skin cancer
One fourth of all cancers in men
The risk of a man being diagnosed with prostate cancer during his lifetime is 1 in 6

36. PROSTATE CANCER – THE SCOPE OF THE PROBLEM
In the U.S., approximately 240,000 men are diagnosed with prostate cancer every year, and approximately 28,000 men die of the disease
The rate of diagnosis of prostate cancer in the U.S. increased dramatically in the early 1990’s, likely due to the institution of widespread screening, but has been leveling off since the mid 1990’s

37. PROSTATE CANCER – THE SCOPE OF THE PROBLEM
Overall, ~12% of patients diagnosed with prostate cancer will die of their disease, but survival rate depends upon how advanced the disease is at diagnosis
Prostate cancer tends to progress much more slowly than other cancers, and even patients with advanced disease may live for many years

38. PROSTATE CANCER – WHAT PUTS YOU AT RISK?
Age
The incidence of prostate cancer increases steadily after age 40
Autopsy studies have shown that up to 80% of men over 70 have prostate cancer at the time of their deaths

39. PROSTATE CANCER – WHAT PUTS YOU AT RISK?
Men with a family history of prostate cancer have an increased risk of developing prostate cancer themselves
In the U.S., African Americans have an ~60% higher incidence of prostate cancer than Caucasians
Environmental and/or dietary factors clearly play a role, but that role is not well understood

40. PROSTATE CANCER PREVENTION
Finasteride and dutasteride
Inhibit the enzyme that converts testosterone to dihydrotestosterone, which is the primary active androgen (male hormone) that acts on the prostate
Decrease the risk of prostate cancer in men over 50 by 20-25% if taken for several years
Also decrease benign prostate enlargement and combat hair loss
Not FDA approved for prostate cancer prevention, and not widely used for this purpose

41. PROSTATE CANCER DIAGNOSIS
The majority of patients are diagnosed due to screening, and are entirely asymptomatic
As the disease progresses within the prostate, patients may develop recurrent urinary tract infections, blood in the urine or inability to urinate
Urinary tract infections are uncommon in men and generally should lead to an evaluation for an underlying cause
Prostate cancer spreads primarily to bone, so patients with advanced disease may have bone pain

42. PROSTATE CANCER SCREENING
Very controversial – unclear if screening decreases the risk of dying of prostate cancer or not, as studies examining this subject have yielded conflicting results
In 2011, the USPSTF recommended against screening for prostate cancer, but other medical societies continue to recommend offering screening

43. PROSTATE CANCER SCREENING
A large European study reported in 2009 which randomly assigned men to either undergo or not undergo PSA screening did show a decreased risk of death from prostate cancer in men who underwent PSA screening than in men who did not*
A similar study performed in the U.S. did not show a similar benefit, but ~50% of the men assigned to no screening were undergoing PSA screening outside of the study, which could have obscured any benefit**
*Schroder et al., N Engl J Med 2009, v. 360, 1320; **Andriole et al., N Engl J Med 2009, v. 360, 1310

44. PROSTATE CANCER SCREENING
Screening is performed by checking a PSA (prostate specific antigen) level in the blood, and examining the prostate gland
When performed, screening generally starts at age 50

45. PROSTATE CANCER SCREENING
What’s the harm?
Many men with prostate cancer will never have symptoms from the cancer during their lifetimes, and will not die of the disease even with no therapy
There is no doubt that many men with prostate cancer receive unnecessary therapy with potentially serious side effects

46. PROSTATE CANCER MANAGEMENT
“Watchful waiting”, or observation without treatment, is a reasonable option for men with low risk disease
Small tumors
Low grade tumors (i.e. tumors whose microscopic appearance more closely resembles normal prostate tissue)
Low PSA levels
Treatment should be offered if there is evidence that the cancer is progressing

47. PROSTATE CANCER TREATMENT – LOCALIZED DISEASE
Surgical removal of the prostate (radical prostatectomy)
Main risks are erectile dysfunction and urinary incontinence
Radiation to the prostate
Can also cause erectile dysfunction
May cause long term inflammation of the bladder and rectum
Surgery and radiation are likely equivalent in effectiveness

48. PROSTATE CANCER TREATMENT – LOCALIZED DISEASE
Patients who are at high risk of recurrence are also offered additional therapy with androgen deprivation

49. PROSTATE CANCER TREATMENT – ADVANCED DISEASE
Primary therapy is always androgen deprivation, i.e. decreasing testosterone levels
Surgical castration
Medications which shut down testosterone production by the testes
In theory reversible, in practice often not reversible, especially in elderly men
Androgen deprivation is highly effective, but the effect is almost always temporary

50. PROSTATE CANCER TREATMENT – ADVANCED DISEASE
Treatment options for prostate cancer resistant to testosterone deprivation
Chemotherapy
Immunotherapy

51. TESTICULAR CANCER – THE SCOPE OF THE PROBLEM
Testicular cancer is rare overall, but is the most common cancer in young men, and is one of the most highly curable cancers
There are approximately 8600 cases of testicular cancer per year in the U.S., but only approximately 360 deaths per year
Most commonly affects men age 15-45, but there is a small secondary peak in incidence after age 60

52. TESTICULAR CANCER – WHAT PUTS YOU AT RISK?
Previous cancer in the opposite testis
Approximately 1-4% of pts with testicular cancer will develop cancer in the remaining testis
Cryptorchidism (non-descended testes) is associated with a several fold increased risk of testicular cancer
5-20% of cases actually occur in the normally descended testicle
Family history is likely associated with a slightly increased risk

53. TESTICULAR CANCER – WHAT PUTS YOU AT RISK?
DES exposure in utero increases the risk of cryptorchidism but may not independently increase the risk of testicular cancer
Some studies suggest that HIV infection increases the risk of testicular cancer
Other viral infections, trauma and vasectomy do not seem to increase risk

54. TESTICULAR CANCER PREVENTION
The only known preventive measure is surgical correction of cryptorchidism

55. TESTICULAR CANCER DIAGNOSIS
No established role for routine screening
Most common presentation is a painless testicular mass
Patients with advanced disease can present with symptoms related to spread of the cancer, such as cough, abdominal pain, back pain or neurologic symptoms

56. TESTICULAR CANCER TREATMENT
Varies by subtype of testicular cancer
Seminoma
Overall better prognosis
More sensitive to radiation
Nonseminoma
Long term survival rate is 95+%

57. TESTICULAR CANCER TREATMENT
Orchiectomy, or surgical removal of the affected testis, is always indicated and is the primary treatment for localized disease
Approximately 25% of patients with localized disease will relapse, but most of these patients will still be cured with further therapy

58. TESTICULAR CANCER TREATMENT – OPTIONS FOR LOCALIZED DISEASE
For both seminoma and nonseminoma, options include
Observation after surgery, with additional treatment only in the event of relapse
Requires a compliant patient
A short course of chemotherapy – one single dose to six weeks, depending upon the circumstances

59. TESTICULAR CANCER TREATMENT – ADDITIONAL OPTIONS FOR LOCALIZED DISEASE
Seminoma
Radiation to the lymph nodes that drain the testis
Nonseminoma
Surgical removal of the draining lymph nodes

60. TESTICULAR CANCER TREATMENT –DISEASE IN THE REGIONAL LYMPH NODES
Seminoma
A longer course of chemotherapy – 9-12 weeks
Radiation to the lymph nodes
Nonseminoma
Surgical removal of the involved lymph nodes

61. TESTICULAR CANCER TREATMENT – ADVANCED DISEASE
A longer course of chemotherapy, 9-12 weeks
Length of treatment depends upon factors such as the location of metastasis (spread)
Cure rate varies from 50-90%

62. CONCLUSIONS
Advances in cancer diagnosis and treatment include high-tech diagnostic studies, drugs which required many years of laboratory research (and $$$$) to develop, such as Herceptin, and low-tech interventions like reducing dietary fat intake
As a result of these advances, cancer is more treatable, and curable, than ever, and we continue to make strides in combating cancer every year

63. ACKNOWLEDGMENTS
Dr. Ruth Williamson provided some of the slides used in this presentation