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“П’ЯТИЙ ЧЕРКАСЬКИЙ МІСЬКИЙ ЦЕНТР МЕДИКО-САНІТАРНОЇ ДОПОМОГИ”

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Clinic

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вул. 30 років Перемоги, 20

E-mail: clinica5@medicine.ck.ua

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Which Cancer Tests Do You Really Need?

By Kathleen Doheny

From the WebMD Archives

Feb. 1, 2013 -- Not all cancer screening tests are helpful, and some are potentially harmful, according to a new Consumer Reports rating.

In the new report, Consumer Reports recommends only three of 11 common cancer screening tests, and then only for certain age groups.

Screenings for cervical, colon, and breast cancer are recommended.

Screenings for cancers affecting the bladder, lungs, skin, mouth, prostate, ovaries, pancreas, and testicles are not.

"The science of prevention and screening has changed," says John Santa, MD, MPH, director of the Consumer Reports Health Ratings Center. He oversaw the project.

"Consumers need to know that some screening tests are terrific, some are not good, and some can harm you," Santa says.

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"We are not talking about people at high risk," he says. "And of course they are not symptomatic. We're not talking about what you should do if you have a mole that is changing or if you feel a breast lump."

The full report is in the March issue of Consumer Reports.

Cancer Screening: CR Ratings

To develop the ratings, Santa and his team looked at medical research, consulted medical experts, surveyed more than 10,000 readers, and talked with patients about screening tests.

They looked closely at recommendations of the U.S. Preventive Services Task Force. This independent panel provides guidelines on health care based on evidence. Much of Consumer Reports' recommendations follow the task force guidelines to the letter. But, their recommendations sometimes differ from those of organizations such as the American Cancer Society (ACS). Here, details on the three recommended tests:




·      Cervical cancer . Women 21 to 30 should have a Pap smear to test for cervical cancer every three years. Women 30 to 65 can wait five years if they have had testing for human papillomavirus (HPV), the virus that causes the cancer. Those 65-plus can skip screening if they were screened regularly earlier. Those under 21 can also skip the test, as experts know the cancer is not common at those ages.

·      Colon cancer. Those 50 to 75 should get screened regularly, and older people should discuss the pros and cons with their doctor and decide. Options include a colonoscopy, which examines the entire colon, every 10 years, or a sigmoidoscopy, which looks at the lower third, every five years plus a stool test every three years, or an annual stool test. As far as other guidelines, no groups suggest screening younger than 50 unless high risk. The ACS also doesn't say to specifically stop at age 75.

·      Breast cancer . Women 50 to 75 need a mammogram every two years. Those 40 to 49 or 75 and older should talk with their doctor about pros and cons. These guidelines do split with those of the ACS, though. The cancer society recommends yearly mammograms after age 40 and as long as healthy.

·       

Which Cancer Tests Do You Really Need?

By Kathleen Doheny

From the WebMD Archives

Continued

The other eight tests were not recommended for those not at high risk because the cancers are uncommon, the test's effectiveness is not proven, or the test can't detect the disease at a curable stage. And even though some of the tests aren't really recommended by anyone, this list is a valuable reminder for people who may feel they need to seek them out.

On the "avoid" list, screenings for:

·      Bladder cancer. The test looks for blood or cancer cells in the urine.

·      Lung cancer. The test is a low-dose CT scan. The ACS only recommends this for high-risk people (such as older individuals who've smoked for years).

·      Skin cancer. The test is a visual exam of your skin to spot signs of the deadly skin cancer melanoma. The ACS says a skin exam by a doctor should be included as part of the routine check-up.

·      Oral cancer. This visual exam of the mouth is done by a dentist or other health care professional. The ACS suggests this as part of your normal routine oral care.

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·      Prostate cancer. The blood test is known as the PSA (prostate-specific antigen) test. The ACS says to discuss PSA tests with your doctor, but doesn’t recommend widespread screening of everyone.

·      Ovarian cancer. Tests include a blood test to look for a protein linked with the cancer, and a transvaginal ultrasound. This test is generally not recommended by anyone for the general public.

·      Pancreatic cancer. Tests are abdominal images or genetic tests. This test is also generally not recommended by anyone for the general public.

·      Testicular cancer. The test is a physical exam of the testicles. ACS does recommend this as part of routine care; the task force doesn't.




Cancer Tests: Perspectives

The new ratings drew mixed reactions.

Otis Brawley, MD, chief medical officer of the American Cancer Society, says the report helps to put screening into its proper perspective. "There has been a significant amount of over-promising and over-promoting," he says.

He frowns on aggressive campaigns that have included mammogram parties or group colonoscopies.

Which Cancer Tests Do You Really Need?

By Kathleen Doheny

From the WebMD Archives

Continued

"A lot of screening is being done by organizations that can profit from it," he says.

"The truth is, certain tests do have some significant benefit, and every test has some limitations," he says. "In the spirit of informed decision-making, people need to understand both the potential for benefit and the potential for harm."

As mentioned, the recommendations on breast cancer screening from Consumer Reports and the American Cancer Society are different, but Brawley calls these differences ''minimal."

"We recommend women in their 40s get a mammogram on an annual basis, but we also recommend those women get information on the limitations," he says.

These include missing some cancers and ordering additional tests when no cancer turns out to be there.

Some doctors took issue with the decision to use the task force recommendations as the basic source.

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"I'm disappointed they followed the task force guidelines, because we feel they are inadequate to protect women," says Debra Monticciolo, MD, chair of the American College of Radiology's Quality and Safety Commission and vice chair of radiology at Scott & White Healthcare in Temple, Texas.

"Right now, we can't cure breast cancer, so we really need to find cancers early," she says. Research has found the best way to do that is by yearly mammograms beginning at age 40, she says.

The recommendation to avoid PSA tests refutes evidence that they work, say Dipen Parekh, MD, a professor and chair of urology at the University of Miami Miller School of Medicine's Sylvester Comprehensive Cancer Center.




"There is no question the decline in the incidence of advanced prostate cancer is due in large part to PSA screening," he says.

However, the recommendation for women at low risk for ovarian cancer not to seek screening is a good one, says J. Matt Pearson, MD, assistant professor and a gynecologic oncologist at the University of Miami Miller School of Medicine's Sylvester Comprehensive Cancer Center.

The lifetime risk of ovarian cancer in the general population is low. When you screen for a cancer that is not common, he tells women, "you are more likely to find a benign abnormality that pushes you toward [unneeded] surgery."

ontinued

Cancer Tests: Making the Decision

Santa recommends educating yourself about cancer screening tests, then talking to your doctor about whether the benefits outweigh the risks for you.

"Don't go to a mobile van, don't go to a mammogram party," he says.

"Don't believe a billboard on the highway that tells you to get a PSA test when it comes from a hospital that has a robotic prostate cancer surgery program."

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Cancer Prevention: Lifestyle, Lifestyle, Lifestyle

"If you are serious about preventing cancer, you don't smoke, you exercise, and you try to get to a normal weight," Santa says. Obesity has been linked with about 4% of men's new cancers and 7% of women's, he says.

Getting to a normal weight may especially lower the risk for uterine and esophageal cancers.

Regular exercise can reduce colon and breast cancer risk.




Smoking is linked with lung cancer as well as cancers of the larynx, oral cavity, esophagus, bladder, kidney, and pancreas.

 


Breast Cancer

·      General references

·      Risk Factors

·      Risk factors references

·      Pathology

·      Pathophysiology

·      Hormone receptors

·      Symptoms and Signs

·      Screening

·      Mammography

·      Breast examination

·      MRI

·      Screening references

·      Diagnosis

·      Biopsy

·      Evaluation after cancer diagnosis

·      Grading and staging

·      Prognosis

·      Treatment

·      Surgery

·      Lymph node evaluation

·      Reconstructive procedures

·      Radiation therapy

·      Adjuvant systemic therapy

·      Metastatic disease

·      End-of-life issues

·      Treatment references

·      Prevention

·      Key Points

·      More Information

·      Resources In This Article

·      Drugs Mentioned In This Article

Also of Interest

·      (Quiz) Uterine and Vaginal Prolapse

·      (News) Faster Delivery for Induction With Misoprostol Plus Cervical Foley

·      (News) Dense-Dose Chemo of Little Benefit in Early Breast Cancer

·      (News) Blood Test May Help ID Risk of Fetal Alcohol Spectrum Disorders

·      (News) Protein Intake Tied to Modest Survival Advantage in Breast CA

·      (News) Self-Harm Now a Leading Cause of Pregnancy-Related Mortality

·      (Video) Overview of Placenta Previa

Breast Cancer

By Mary Ann Kosir, MD, Professor of Surgery and Oncology;, Wayne State University School of Medicine;Karmanos Cancer Center

Click here for
Patient Education

NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version

·      Breast Disorders

·      Evaluation of Breast Disorders

·      Breast Cancer

·      Breast Masses (Breast Lumps)

·      Mastalgia (Breast Pain)

·      Nipple Discharge

·      Phyllodes Tumor

 

Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis is confirmed by biopsy. Treatment usually includes surgical excision, often with radiation therapy, with or without adjuvant chemotherapy, hormonal therapy, or both.

In the US, breast cancer is the 2nd leading cause of cancer death in white, black, Asian/Pacific Islander, and American Indian/Alaska Native women (after lung/bronchial cancer) but is the leading cause of cancer death among Hispanic women (1).

About 253,000 new cases of invasive breast cancer and about 41,000 deaths from it are expected in 2017. In addition, about 63,000 new cases of in situ breast cancer are expected in 2017 (2).

Male breast cancer accounts for about 1% of total cases; about 2500 new cases of invasive breast cancer and > 450 deaths from it are expected in 2017. In men, manifestations, diagnosis, and management are the same, although men tend to present later.

General references

·      1. National Cancer Institute: Cancer Among Women. Accessed 1/18/18.

·      2. American Cancer Society: Breast Cancer Facts and Figures 2017–2018. Atlanta: American Cancer Society, Inc. 2017. Accessed on 1/18/18.

Risk Factors

For women in the US, cumulative risk of developing breast cancer is 12% (1 in 8) by age 95. Much of the risk is incurred after age 60 (see Table: Risk of Being Diagnosed With Invasive Breast Cancer). These statistics can be misleading because most people die before age 95, and cumulative risk of developing the cancer in any 20-yr period is considerably lower. Risk of dying of breast cancer is about 9% 5 yr after diagnosis (1).


Risk of Being Diagnosed With Invasive Breast Cancer

Age (yr)

10-yr Risk (%)

20-yr Risk (%)

30-yr Risk (%)

Lifetime Risk (%)

Lifetime Risk of Dying of Invasive Breast Cancer (%)

30

0.5

1.9

4.1

12.6

2.7

40

1.5

3.7

6.8

12.3

2.6

50

2.3

5.5

8.8

11.1

2.5

60

3.5

6.9

8.9

9.4

2.3

70

4.0

6.2

6.8

2.0

Data from 2012–14. Based on the seer.cancer.gov web site. Accessed on 1/18/18.


Factors that may affect breast cancer risk include the following:

·      Age: The strongest risk factor for breast cancer is age. Most breast cancers occur in women > 50.

·      Family history: Having a 1st-degree relative (mother, sister, daughter) with breast cancer doubles or triples risk of developing the cancer, but breast cancer in more distant relatives increases risk only slightly. When ≥ 2 1st-degree relatives have breast cancer, risk may be 5 to 6 times higher.

·      Breast cancer gene mutation: About 5 to 10% of women with breast cancer carry a mutation in one of the 2 known breast cancer genes, BRCA1 or BRCA2. If relatives of such a woman also carry the mutation, they have a 50 to 85% lifetime risk of developing breast cancer. Women with BRCA1 mutations also have a 20 to 40% lifetime risk of developing ovarian cancer; risk among women with BRCA2 mutations is increased less. Women without a family history of breast cancer in at least 2 1st-degree relatives are unlikely to carry this mutation and thus do not require screening for BRCA1 and BRCA2 mutations. Men who carry a BRCA2 mutation also have an increased risk of developing breast cancer. The mutations are more common among Ashkenazi Jews. Women with BRCA1 or BRCA2 mutations may require closer surveillance or preventive measures, such as taking tamoxifen or raloxifene or undergoing double mastectomy.

·      Personal history: Having had in situ or invasive breast cancer increases risk. Risk of developing cancer in the contralateral breast after mastectomy is about 0.5 to 1%/yr of follow-up.

·      Gynecologic history: Early menarche, late menopause, or late first pregnancy increases risk. Women who have a first pregnancy after age 30 are at higher risk than those who are nulliparous.

·      Breast changes: History of a lesion that required a biopsy increases risk slightly. Women with multiple breast masses but no histologic confirmation of a high-risk pattern should not be considered at high risk. Benign lesions that may slightly increase risk of developing invasive breast cancer include complex fibroadenoma, moderate or florid hyperplasia (with or without atypia), sclerosing adenosis, and papilloma. Risk is about 4 or 5 times higher than average in patients with atypical ductal or lobular hyperplasia and about 10 times higher if they also have a family history of invasive breast cancer in a 1st-degree relative. Increased breast density seen on screening mammography is associated with an increased risk of breast cancer.

·      Lobular carcinoma in situ (LCIS): Having LCIS increases the risk of developing invasive carcinoma in either breast by about 25 times; invasive carcinoma develops in about 1 to 2% of patients with LCIS annually.

·      Use of oral contraceptives: Oral contraceptive use increases risk very slightly (by about 5 more cases per 100,000 women). Risk increases primarily during the years of contraceptive use and tapers off during the 10 yr after stopping. Risk is highest in women who began to use contraceptives before age 20 (although absolute risk is still very low).

·      Hormone therapy: Postmenopausal hormone (estrogen plus a progestin) therapy appears to increase risk modestly after only 3 yr of use (2). After 5 yr of use, the increased risk is about 7 or 8 more cases per 10,000 women for each year of use (about a 24% increase in relative risk). Use of estrogen alone does not appear to increase risk of breast cancer (as reported in the Women's Health Initiative). Selective estrogen-receptor modulators (eg, raloxifene) reduce the risk of developing breast cancer.

·      Radiation therapy: Exposure to radiation therapy before age 30 increases risk. Mantle-field radiation therapy for Hodgkin lymphoma about quadruples risk of breast cancer over the next 20 to 30 yr.

·      Diet: Diet may contribute to development or growth of breast cancers, but conclusive evidence about the effect of a particular diet (eg, one high in fats) is lacking. Obese postmenopausal women are at increased risk, but there is no evidence that dietary modification reduces risk. For obese women who are menstruating later than normal, risk may be decreased.

·      Lifestyle factors: Smoking and alcohol may contribute to a higher risk of breast cancer. Women are counseled to stop smoking and to reduce alcohol consumption.

The Breast Cancer Risk Assessment Tool (BCRAT), or Gail model, can be used to calculate a women's 5-yr and lifetime risk of developing breast cancer.

Risk factors references

·      1. American Cancer Society: Breast Cancer Facts and Figures 2017–2018. Atlanta: American Cancer Society, Inc. 2017. Accessed on 1/18/18.

·      2. Writing Group for the Women's Health Initiative Investigators: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA 288 (3):321–333, 2002.

Pathology

Most breast cancers are epithelial tumors that develop from cells lining ducts or lobules; less common are nonepithelial cancers of the supporting stroma (eg, angiosarcoma, primary stromal sarcomas, phyllodes tumor).

Cancers are divided into carcinoma in situ and invasive cancer.

Carcinoma in situ is proliferation of cancer cells within ducts or lobules and without invasion of stromal tissue. There are 2 types:

·      Ductal carcinoma in situ (DCIS): About 85% of carcinoma in situ are this type. DCIS is usually detected only by mammography. It may involve a small or wide area of the breast; if a wide area is involved, microscopic invasive foci may develop over time.

·      Lobular carcinoma in situ (LCIS): LCIS is often multifocal and bilateral. There are 2 types: classic and pleomorphic. Classic LCIS is not malignant but increases risk of developing invasive carcinoma in either breast. This nonpalpable lesion is usually detected via biopsy; it is rarely visualized with mammography. Pleomorphic LCIS behaves more like DCIS; it should be excised to negative margins.

Invasive carcinoma is primarily adenocarcinoma. About 80% is the infiltrating ductal type; most of the remaining cases are infiltrating lobular. Rare types include medullary, mucinous, metaplastic, and tubular carcinomas. Mucinous carcinoma tends to develop in older women and to be slow growing. Women with these types of breast cancer have a much better prognosis than women with other types of invasive breast cancer.

Inflammatory breast cancer is a fast-growing, often fatal cancer. Cancer cells block the lymphatic vessels in breast skin; as a result, the breast appears inflamed, and the skin appears thickened, resembling orange peel (peau d’orange). Usually, inflammatory breast cancer spreads to the lymph nodes in the armpit. The lymph nodes feel like hard lumps. However, often no mass is felt in the breast itself because this cancer is dispersed throughout the breast.

Paget disease of the nipple (not to be confused with the metabolic bone disease also called Paget disease) is a form of ductal carcinoma in situ that extends into the skin over the nipple and areola, manifesting with a skin lesion (eg, an eczematous or a psoriaform lesion). Characteristic malignant cells called Paget cells are present in the epidermis. Women with Paget disease of the nipple often have underlying invasive or in situ cancer.


 

Paget Disease of the Nipple

DR M.A. ANSARY/SCIENCE PHOTO LIBRARY


Pathophysiology

Breast cancer invades locally and spreads through the regional lymph nodes, bloodstream, or both. Metastatic breast cancer may affect almost any organ in the body—most commonly, lungs, liver, bone, brain, and skin.

Most skin metastases occur near the site of breast surgery; scalp metastases are also common. Metastatic breast cancer frequently appears years or decades after initial diagnosis and treatment.

Hormone receptors

Estrogen and progesterone receptors, present in some breast cancers, are nuclear hormone receptors that promote DNA replication and cell division when the appropriate hormones bind to them. Thus, drugs that block these receptors may be useful in treating tumors with the receptors. About two thirds of postmenopausal patients with cancer have an estrogen-receptor positive (ER+) tumor. Incidence of ER+ tumors is lower among premenopausal patients.

Another cellular receptor is human epidermal growth factor receptor 2 (HER2; also called HER2/neu or ErbB2); its presence correlates with a poorer prognosis at any given stage of cancer. In about 20% of patients with breast cancer, HER2 receptors are overexpressed. Drugs that block these receptors are part of standard treatment for these patients.

Symptoms and Signs

Many breast cancers are discovered as a mass by the patient or during routine physical examination or mammography. Less commonly, the presenting symptom is breast pain or enlargement or a nondescript thickening in the breast.

Paget disease of the nipple manifests as skin changes, including erythema, crusting, scaling, and discharge; these changes usually appear so benign that the patient ignores them, delaying diagnosis for a year or more. About 50% of patients with Paget disease of the nipple have a palpable mass at presentation.

A few patients with breast cancer present with signs of metastatic disease (eg, pathologic fracture, pulmonary dysfunction).

A common finding during physical examination is asymmetry or a dominant mass—a mass distinctly different from the surrounding breast tissue. Diffuse fibrotic changes in a quadrant of the breast, usually the upper outer quadrant, are more characteristic of benign disorders; a slightly firmer thickening in one breast but not the other may be a sign of cancer.

More advanced breast cancers are characterized by one or more of the following:

·      Fixation of the mass to the chest wall or to overlying skin

·      Satellite nodules or ulcers in the skin

·      Exaggeration of the usual skin markings resulting from skin edema caused by invasion of dermal lymphatic vessels (so-called peau d’orange)

Matted or fixed axillary lymph nodes suggest tumor spread, as does supraclavicular or infraclavicular lymphadenopathy.

Inflammatory breast cancer is characterized by peau d'orange, erythema, and enlargement of the breast, often without a mass. A nipple discharge is common. Inflammatory breast cancer has a particularly aggressive course.


 

 

Inflammatory Breast Cancer

MID ESSEX HOSPITAL SERVICES NHS TRUST/SCIENCE PHOTO LIBRARY


Screening

All women should be screened for breast cancer (1). All professional societies and groups agree on this concept, although they differ on the recommended age at which to start screening and the precise frequency of screening.

Screening modalities include

·      Mammography (including digital and 3-dimensional)

·      Clinical breast examination (CBE) by health care practitioners

·      MRI (for high-risk patients)

·      Monthly breast self-examination (BSE)

Mammography

In mammography, low-dose x-rays of both breasts are taken in 1 (oblique) or 2 views (oblique and craniocaudal).

Mammography is more accurate in older women, partly because with aging, fibroglandular tissue in breasts tends to be replaced with fatty tissue, which can be more easily distinguished from abnormal tissue. Mammography is less sensitive in women with dense breast tissue, and some states mandate informing patients that they have dense breast tissue when it is detected by screening mammography.

Screening mammography guidelines for women with average risk of breast cancer vary, but generally, screening starts at age 40, 45, or 50 and is repeated every year or two until age 75 or life expectancy is < 10 yr (see Table: Recommendations for Breast Cancer Screening Mammography in Women With Average Risk). Clinicians should make sure that patients understand what their individual risk of breast cancer is and ask patients what their preference for testing is.


Recommendations for Breast Cancer Screening Mammography in Women With Average Risk

Recommendations

USPSTF

ACS

ACP

AAFP

ACOG

ACR

NCCN

Initiation age (yr)

50*

45

50*

50*

40

40

40

Frequency (yr)

2

Yearly until age 54, then every 2 yr

1–2

2

1

1

1

Cessation age (yr)

75

When life expectancy is < 10 yr

75

75

75†

75†

75†

*Women aged 40–50: Counseling about risks and benefits of mammography is recommended, and testing may be done based on risk and patient preference.

†Women age ≥ 75: Screening may be done if life expectancy is good or the patient requests it.

AAFP = American Academy of Family Physicians; ACOG = American College of Obstetricians and Gynecologists; ACP = American College of Physicians; ACR = American College of Radiology; ACS = American Cancer Society; NCCN = National Comprehensive Cancer Network; USPSTF = US Preventive Services Task Force.


The Breast Cancer Risk Assessment Tool (BCRAT), or Gail model, can be used to calculate a woman's 5-yr and lifetime risk of developing breast cancer. A woman is considered at average risk if her lifetime risk of breast cancer is < 15%.

Clinical Calculator: Gail Model for 5 Year Risk of Breast Cancer in Black Women (2007)

Clinical Calculator: Gail Model for 5 Year Risk of Breast Cancer (1999 paper)

Concerns about when and how often to do screening mammography include

·      Accuracy

·      Risks and costs

Only about 10 to 15% of abnormalities detected on screening mammography result from cancer—an 85 to 90% false-positive rate. False-negative results may exceed 15%. Many of the false-positives are caused by benign lesions (eg, cysts, fibroadenomas), but there are new concerns about detecting lesions that meet histologic definitions of cancer but do not develop into invasive cancer during a patient's lifetime.

Accuracy depends partly on the techniques used and experience of the mammographer. Some centers use computer analysis of digitized mammography images (full-field digital mammography) to help in diagnosis. Such systems may be slightly more sensitive for invasive cancers in women < 50 when results are interpreted by radiologists, but probably not when interpreted primarily via computer detection.

Breast tomosynthesis (3-dimensional mammography), done with digital mammography, increases the rate of cancer detection slightly and decreases the rate of recall imaging (2); this test is helpful for women with dense breast tissue. However, the test exposes women to almost twice as much radiation as traditional mammography.

Although mammography uses low doses of radiation, radiation exposure has cumulative effects on cancer risk. When radiologic screening is started at a young age, risk of cancer is increased.

Costs include not only the cost of imaging itself but the costs and risks of diagnostic tests needed to evaluate false-positive imaging results.

Breast examination

The value of routine clinical or breast self-examination remains controversial. Some societies such as the American Cancer Society and the US Preventive Services Task Force recommend against either modality for routine screening in average-risk women. Other societies including the American College of Obstetricians and Gynecologists advocate clinical and breast self-examination as important components of screening for breast cancer.

Clinical breast examination (CBE) is usually part of routine annual care for women > 40 (1). In the US, CBE augments rather than replaces screening mammography. However, in some countries where mammography is considered too expensive, CBE is the sole screen; reports on its effectiveness in this role vary.

Breast self-examination (BSE) alone has not been shown to reduce mortality rate, but evidence of its usefulness is mixed, and it is widely practiced. Because a negative BSE may tempt some women to forego mammography or CBE, the need for these procedures should be reinforced when BSE is taught. Patients should be instructed to do BSE on the same day each month. For menstruating women, 2 or 3 days after menses ends is recommended because breasts are less likely to be tender and swollen.


 

Breast Self-Examination (3 Methods)


MRI

MRI is thought to be better than CBE or mammography for screening women with a high (eg, > 20%) risk of breast cancer, such as those with a BRCA gene mutation. For these women, screening should include MRI as well as mammography and CBE. MRI has higher sensitivity but may be less specific. Because specificity is lower, MRI is not considered appropriate for screening women with average or slightly increased risk.

Screening references

·      1. The American College of Obstetricians and Gynecologists: Practice bulletin no. 122: Breast cancer screening. Obstet Gynecol 118 (2), part 1:372–382, 2011.

·      2. Friedewald SM, Rafferty EA, Rose SL, et al: Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA 311 (24):2499–2507, 2014. doi: 10.1001/jama.2014.6095.

Diagnosis

·      Screening by mammography, breast examination, and imaging (eg, ultrasonography)

·      Biopsy, including analysis for estrogen and progesterone receptors and for HER2 protein

Testing is required to differentiate benign lesions from cancer. Because early detection and treatment of breast cancer improves prognosis, this differentiation must be conclusive before evaluation is terminated.

If advanced cancer is suspected based on physical examination, biopsy should be done first; otherwise, the approach is the same as evaluation for a breast mass, which typically includes ultrasonography. All lesions that could be cancer should be biopsied. A prebiopsy bilateral mammogram may help delineate other areas that should be biopsied and provides a baseline for future reference. However, mammogram results should not alter the decision to do a biopsy if that decision is based on physical findings.


Pearls & Pitfalls

·      Mammogram results should not alter the decision to do a biopsy if that decision is based on physical findings.


Biopsy

Percutaneous core needle biopsy is preferred to surgical biopsy. Core biopsy can be done guided by imaging or palpation (freehand). Routinely, stereotactic biopsy (needle biopsy guided by mammography done in 2 planes and analyzed by computer to produce a 3-dimensional image) or ultrasound-guided biopsy is being used to improve accuracy. Clips are placed at the biopsy site to identify it.

If core biopsy is not possible (eg, the lesion is too posterior), surgical biopsy can be done; a guidewire is inserted, using imaging for guidance, to help identify the biopsy site.

Any skin taken with the biopsy specimen should be examined because it may show cancer cells in dermal lymphatic vessels.

The excised specimen should be x-rayed, and the x-ray should be compared with the prebiopsy mammogram to determine whether all of the lesion has been removed. If the original lesion contained microcalcifications, mammography is repeated when the breast is no longer tender, usually 6 to 12 wk after biopsy, to check for residual microcalcifications.

Evaluation after cancer diagnosis

After cancer is diagnosed, a multidisciplinary evaluation is usually done to plan further testing and treatment. The core multidisciplinary team typically includes a breast surgical oncologist, medical oncologist, and radiation oncologist plus other experts in cancer (tumor board).

Part of a positive biopsy specimen should be analyzed for estrogen and progesterone receptors and for HER2 protein.

Cells from blood or saliva should be tested for BRCA1 and BRCA2 genes when

·      Family history includes multiple cases of early-onset breast cancer.

·      Ovarian cancer develops in patients with a family history of breast or ovarian cancer.

·      Breast and ovarian cancers occur in the same patient.

·      Patients have an Ashkenazi Jewish heritage.

·      Family history includes a single case of male breast cancer.

·      Breast cancer develops at age < 45.

·      The cancer does not have estrogen or progesterone receptors or overexpression of HER2 protein (triple negative breast cancer).

For these tests, the best approach is to refer patients to a genetic counselor, who can document a detailed family history, choose the most appropriate tests and help interpret the results.

Chest x-ray, CBC, liver function tests, and measurement of serum calcium levels should be done to check for metastatic disease.

An oncologist should be consulted to determine whether to measure serum carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, or CA 27-29 and whether bone scanning should be done.

For bone scanning, common indications include the following:

·      Bone pain

·      Elevated serum alkaline phosphatase

·      Stage III or IV cancer

Abdominal CT is done if patients have any of the following:

·      Abnormal liver function results

·      Abnormal abdominal or pelvic examination

·      Stage III or IV cancer

Chest CT is done if patients have either of the following:

·      Pulmonary symptoms such as shortness of breath

·      Stage III or IV cancer

MRI is often used by surgeons for preoperative planning; it can accurately determine tumor size, chest wall involvement, and number of tumors.

Grading and staging

Grading is based on histologic examination of the tissue taken during biopsy.

Staging follows the TNM (tumor, node, metastasis) classification (see Table: Staging of Breast Cancer*). Because clinical examination and imaging have poor sensitivity for nodal involvement, staging is refined during surgery, when regional lymph nodes can be evaluated. However, if patients have palpably abnormal axillary nodes, preoperative ultrasonography-guided fine needle aspiration or core biopsy may be done:

·      If results are positive, axillary lymph node dissection is typically done during the definitive surgical procedure.

·      If results are negative, a sentinel lymph node biopsy, a less aggressive procedure, may be done instead.


Staging of Breast Cancer*

Stage

Tumor

Regional Lymph Node/Distant Metastasis†

0

Tis

N0/M0

IA

T1

N0/M0

IB

T0

N1mi/M0

 

T1‡*

N1mi/M0

IIA

T0

N1§M0

 

T1‡*

N1§/M0

 

T2

N0/M0

IIB

T2

N1/M0

 

T3

N0/M0

IIIA

TI

N2/M0

 

T2

N2/M0

 

T3

N1/M0

 

T3

N2/M0

IIIB

T4

N0/M0

 

T4

N1/M0

 

T4

N2/M0

IIIC

Any T

N3/M0

IV

Any T

Any N/M1

*For more information, see Giuliano AE, Connolly JI, Edge SB, et al: Breast Cancer—Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 67 (4):290-303, 2017. doi: 10.3322/caac.21393 and the American Joint Committee on Cancer's 8th Edition Updates and Corrections. Accessed 1/18/18.

†Classification of regional lymph nodes (N) is divided into clinical (cN) and pathologic (pN), which have slightly different descriptions.

‡T1 includes T1mi.

§Here, N1 excludes N1mi.

Tis = ductal carcinoma in situ or Paget disease of the nipple with no tumor (Paget disease with a tumor is classified by tumor size); T1 = tumor ≤ 2 cm; T1mi = tumor ≤ 0.1 cm; T2 = tumor > 2 but ≤ 5 cm; T3 = tumor > 5 cm; T4 =any size tumor with extension to chest wall and/or skin and with ulceration or skin nodules or inflammatory cancer.

NX = Nearby nodes not assessable (for example, because removed previously); N0 = no spread to nearby nodes or only isolated tumor cells; N1 = spread to 1–3 ipsilateral movable, low or midaxillary nodes and/or metastases detected by sentinel lymph node biopsy in clinically negative internal mammary lymph nodes (pN1); N1mi = N1 nodes with micrometastases (about 200 cells > 0.2 mm, but none > 2 mm); N2 = any of the following:

·      Spread to ipsilateral low or midaxillary nodes that are fixed or matted, detected by clinical examination (cN2)

·      Spread to 4–9 axillary lymph nodes, detected by testing (pN2)

·      Spread to internal mammary nodes but not axillary nodes as detected by clinical examination or imaging

N3 = any of the following:

·      Spread to ipsilateral internal mammary nodes plus axillary nodes as detected by clinical examination or imaging

·      Spread to infraclavicular nodes

·      Spread to supraclavicular nodes

·      Spread to ≥ 10 axillary lymph nodes

·      Spread to > 3 axillary lymph nodes, detected by sentinel lymph node biopsy in clinically negative internal mammary nodes (pN3)

M0 = no metastases but may include micrometastases (cM0[i+]); M1 = metastases present.

Adapted from the American Joint Committee on Cancer, AJCC Cancer Staging Manual, Eighth Edition (2017). Springer New York, Inc.


Prognosis

Long-term prognosis depends on tumor stage. Nodal status (including number and location of nodes) correlates with disease-free and overall survival better than any other prognostic factor.

The 5-yr survival rate (from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program) depends on cancer stage:

·      Localized (confined to primary site): 98.9%

·      Regional (confined to regional lymph nodes): 85.2%

·      Distant (metastasized): 26.9%

·      Unstaged: 53.2%

Poor prognosis is associated with the following other factors:

·      Young age: Prognosis appears worse for patients diagnosed with breast cancer during their 20s and 30s than for patients diagnosed during middle age.

·      Larger primary tumor: Larger tumors are more likely to be node-positive, but they also confer a worse prognosis independent of nodal status.

·      High-grade tumor: Patients with poorly differentiated tumors have a worse prognosis.

·      Absence of estrogen and progesterone receptors: Patients with ER+ tumors have a somewhat better prognosis and are more likely to benefit from hormone therapy. Patients with progesterone receptors on a tumor may also have a better prognosis. Patients with both estrogen and progesterone receptors on a tumor may have a better prognosis than those who have only one of these receptors, but this benefit is not clear.

·      Presence of HER2 protein: When the HER2 gene (HER2/neu [erb-b2]) is amplified, HER2 is overexpressed, increasing cell growth and reproduction and often resulting in more aggressive tumor cells. Overexpression of HER2 is an independent risk factor for a poor prognosis; it may also be associated with high histologic grade, ER− tumors, greater proliferation, and larger tumor size, which are all poor prognostic factors.

·      Presence of BRCA genes: For any given stage, patients with the BRCA1 gene appear to have a worse prognosis than those with sporadic tumors, perhaps because they have a higher proportion of high-grade, hormone receptor–negative cancers. Patients with the BRCA2 gene probably have the same prognosis as those without the genes if the tumors have similar characteristics. With either gene, risk of a 2nd cancer in remaining breast tissue is increased (to perhaps as high as 40%).