BREAST, PROSTATE AND TESTICULAR CANCER:

AN OVERVIEW

Cynthia L. Martel, M.D., Ph.D.USC Oncology

Pasadena

March 12, 2012

BREAST, PROSTATE AND TESTICULAR CANCER - TOPICS FOR DISCUSSIONIncidence rates

Risk factors

Prevention

Treatment

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

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

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

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

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

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)

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

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

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

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)

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: 1079-85

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: 1079-85

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

BREAST CANCER DIAGNOSIS

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

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

BREAST CANCER SCREENING

Breast self-examination

Breast examination by a health care provider

Mammography

BREAST EXAMINATION

Breast self examination

– No longer routinely recommended

– Studies have failed to prove that it is beneficial

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

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

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 50-74 have a mammogram every 2 years

– Why the change?

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

MAMMOGRAPHY

The change in recommendations was based on a calculation of the number of women age 40-49 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

BREAST CANCER TREATMENT

Surgery

Radiation

Medical therapies– Chemotherapy– Hormonal therapy– Herceptin

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

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

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

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

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

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

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– $$$$$$

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

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

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

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

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

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

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

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

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

PROSTATE CANCER SCREENINGVery 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

PROSTATE CANCER SCREENINGA 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

PROSTATE CANCER SCREENINGScreening 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

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

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 levelsTreatment should be offered if there is evidence that the cancer is progressing

PROSTATE CANCER TREATMENT – LOCALIZED DISEASE

Surgical removal of the prostate (radical prostatectomy)– Main risks are erectile dysfunction and

urinary incontinenceRadiation to the prostate– Can also cause erectile dysfunction– May cause long term inflammation of the

bladder and rectumSurgery and radiation are likely equivalent in effectiveness

PROSTATE CANCER TREATMENT – LOCALIZED DISEASE

Patients who are at high risk of recurrence are also offered additional therapy with androgen deprivation

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 testesIn theory reversible, in practice often not reversible, especially in elderly men

Androgen deprivation is highly effective, but the effect is almost always temporary

PROSTATE CANCER TREATMENT – ADVANCED DISEASE

Treatment options for prostate cancer resistant to testosterone deprivation– Chemotherapy

– Immunotherapy

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

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

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

TESTICULAR CANCER PREVENTION

The only known preventive measure is surgical correction of cryptorchidism

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

TESTICULAR CANCER TREATMENT

Varies by subtype of testicular cancer

– SeminomaOverall better prognosis More sensitive to radiation

– Nonseminoma

Long term survival rate is 95+%

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

TESTICULAR CANCER TREATMENT – OPTIONS FOR LOCALIZED DISEASEFor 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

TESTICULAR CANCER TREATMENT – ADDITIONAL OPTIONS FOR LOCALIZED

DISEASESeminoma– Radiation to the lymph nodes that drain the testis

Nonseminoma– Surgical removal of the draining lymph nodes

TESTICULAR CANCER TREATMENT –DISEASE IN THE REGIONAL LYMPH

NODESSeminoma– A longer course of chemotherapy – 9-12

weeks– Radiation to the lymph nodes

Nonseminoma– A longer course of chemotherapy – 9-12

weeks– Surgical removal of the involved lymph

nodes

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%

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

ACKNOWLEDGMENTS

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