- Clinical Findings
- Pathology
- Risk Factors
- Etiology
- Pathophysiology
- Epidemiology
- Prevention
- Management & Treatment
- Complications
- Prognosis
- Clinical Case Studies
- Study Questions
History
- Breast pain
- Early findings: Single, nontender, firm to hard mass with ill-defined margins;
- Later findings: Skin or nipple retraction; nipple discharge; axillary lymphadenopathy; breast enlargement, redness, edema, brawny induration, peau d'orange, pain, fixation of mass to skin ( dimpling) local swelling,or chest wall.
- Late findings: Ulceration; supraclavicular lymphadenopathy; edema of arm; bone, lung, liver, brain, or other distant metastases.Advanced clinical presentations may include pain and/or fracture from bony metastasis.
Physical Exam
X-ray (Mammogram)
Ultrasound
Ultrasoundultrasound with or without fine-needle aspiration, and/or
ductal lavage and/or ductogram.
Genetic and hormonal receptor testing further differentiates breast cancers.
mammographic abnormalities and no palpable mass.
Essentail Criteria to Establish Diagnosis
intraductal carcinoma
BRCA1 and BRCA2 tumor suppressor genes confer strong risk.
Other risk factors include earlier age of menarche, later age of menopause, nulliparity, and late age of first birth, all reflecting higher total number of ovarian cycles.
Obesity, alcohol use, older age, and decreased physical activity have been linked to breast cancer. 1
Recent studies challenge hormone replacement therapy (HRT) as a risk for breast cancer.
HER2 (human epidermal growth factor receptor 2)
Some genes and the proteins they make can influence how a breast cancer behaves and how it might respond to a specific treatment. Cancer cells from a tissue sample can be tested to see which genes are normal and abnormal. The proteins they make can also be tested.HER2 (human epidermal growth factor receptor 2) is one such gene that can play a role in the development of breast cancer. Your pathology report should include information about HER2 status, which tells you whether or not HER2 is playing a role in the cancer. The HER2 gene is also called the ERBB2 (Erb-B2 receptor tyrosine kinase 2) gene, so you may see it referred to by that name in some studies.
The HER2 gene makes HER2 proteins. HER2 proteins are receptors on breast cells. Normally, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself. But in about 25% of breast cancers, the HER2 gene doesn't work correctly and makes too many copies of itself (known as HER2gene amplification). All these extra HER2 genes tell breast cells to make too many HER2 receptors (HER2 protein overexpression). This makes breast cells grow and divide in an uncontrolled way.
Breast cancers with HER2 gene amplification or HER2 protein overexpression are called HER2-positive in the pathology report. HER2-positive breast cancers tend to grow faster and are more likely to spread and come back compared to HER2-negative breast cancers. But there are medicines specifically for HER2-positive breast cancers.
How your results appear in the report will depend on what test you have. There are four tests for HER2:
- IHC test (ImmunoHistoChemistry): The ImmunoHistoChemistry test finds out if there is too much HER2 protein in the cancer cells. The results of the IHC test can be: 0 (negative), 1+ (also negative), 2+ (borderline), or 3+ (positive — HER2 protein overexpression).
- FISH test (Fluorescence In Situ Hybridization): The Fluorescence In Situ Hybridization test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the FISH test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).
- SPoT-Light HER2 CISH test (Subtraction Probe Technology Chromogenic In Situ Hybridization): The SPoT-Light test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the SPoT-Light test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).
- Inform HER2 Dual ISH test (Inform Dual In Situ Hybridization): The Inform HER2 Dual ISH test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the Inform HER2 Dual ISH test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).
It's important to know which HER2 status test you had. Generally, only cancers that test IHC 3+, FISH positive, SPoT-Light HER2 CISH positive, or Inform HER2 Dual ISH positive respond to the medicines that target HER2-positive breast cancers. An IHC 2+ test result is called borderline. If you have an IHC 2+ result, ask to have the tissue retested with a more precise HER2 test: the FISH test, SPoT-Light HER2 CISH test, or the Inform HER2 Dual ISH test.
Research has shown that some breast cancers that are HER2-positive can become HER2-negative over time. Likewise, a HER2-negative breast cancer can become HER2-positive over time. If the breast cancer comes back in the future as advanced disease, doctors should consider ordering another biopsy and retest the tissue’s HER2 status.
Breast cancer is the second most common cancer in women after skin cancer.
Screening
| 2012 Screening Recommendations | AAFP | ACOG | ACS | USPSTF | Other Guidance |
|---|---|---|---|---|---|
| Breast self - examination (BSE) | Recommend against | May be part of breast self-awareness | 20+: BSE is optional; educate on benefits/ limitations | Insufficient evidence | USPSTF, AAFP, ACS, and ACOG encourage breast self-awareness and/or early reporting of breast changes |
| Clinical breast examination | Insufficient evidence | 40+: annual 20–39: every 1–3 years |
40+: annual 20–39: every 1–3 years |
Insufficient evidence | Use of fingerpads of the middle three fingers, overlapping dime-sized circular motions and sequential application of light, medium, and deep levels of pressure recommended |
| Mammography | 40-49: individualize 50-74: biennial screening 75+, insufficient evidence |
40+ offer annual 75+ individualize |
40 through age of good health: offer annual | <50: individualize 50-74: biennial screening 75+, evidence lacking |
Breast density influences ability to detect |
| MRI | Consider in high risk | Not for normal-risk screen | Not for normal-risk screen | Insufficient evidence for normal-risk screen | MRI may afford very high sensitivity in detecting small masses, but is expensive, associated with IV contrast risks, do not detect all breast cancers that mammography can and is not widely available with guided biopsy |
| High-risk women | Refer high-risk women by family history for genetic counseling and BRCA testing | Early enhanced screen | Annual mammogram + MRI for high-risk women 30+ | Early enhanced screen | High risk considered to be BCRA-positive ± ≥20% risk on a valid prediction model |
Mammography remains the mainstay of screening for breast cancer.
Ultrasonography is commonly used for diagnostic follow-up of an abnormality seen on screening mammography, to clarify features of a potential lesion. Ultrasound is also used in some areas to supplement mammographic screening in women with dense breasts, although data supporting benefit for this are inadequate.
The role of magnetic resonance imaging (MRI) for breast cancer screening is emerging; currently, MRI screening in combination with mammography is only targeted to high-risk patients.
Newer tests, such as tomography, are under evaluation [1].
BRCA testing
had no history of cancer) who were identified with screening performed because of family history, these risk estimates should be generally useful for BRCA carriers identified in the course of such testing. In particular, these findings can inform decisions about surveillance and risk-reduction strategies (including chemoprevention and surgery) for these high-risk women.
Risk for Breast and Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers: Refining Our Estimates
Accurate estimation of age-specific risk for breast and ovarian cancer can facilitate counseling of BRCA mutation carriers. Investigators followed women enrolled in familial cancer registries primarily in the U.K., Holland, and France. Women were recruited into this cohort from 1997 to 2011 and had not undergone risk-reducing breast or gynecologic surgery; follow-up continued until 2013 (median, 5 years). A total of 6036 BRCA1 and 3820 BRCA2 mutation carriers were followed (median age at study entry, 38).
Cumulative risk for breast cancer by age 80 was 72% in BRCA1 carriers and 69% in BRCA2 carriers; for ovarian cancer, cumulative risk was 44% and 17%, respectively. Peak breast cancer incidence occurred at age 41–50 for BRCA1 carriers (28 per 1000 person-years) and age 51–60 (31 per 1000) for BRCA2 carriers. Incidence of ovarian cancer was 3.6 times higher among BRCA1 than BRCA2 carriers, with peak incidence occurring among women aged 61–70 regardless of mutation type. Cumulative risk of contralateral breast cancer 20 years after the first breast cancer diagnosis was 40% for BRCA1 carriers and 26% for BRCA2 carriers. For both BRCA1 and BRCA2 carriers, breast cancer risk rose with the number of first- and second-degree relatives with breast cancer. In contrast, ovarian cancer risk did not vary by family history.
Women positive for the heritable BCRA mutation may benefit from prophylactic tamoxifen and prophylactic total mastectomy. Women whose family history is associated with an increased risk for BRCA mutation are referred for genetic counseling and evaluation for BRCA testing.
Indications for genetic referral for BRCA testing.1
- A first-degree relative with breast cancer before age 40
- Two or more relatives with breast or ovarian cancer at any age
- Three or more relatives with breast, ovarian, or colon cancer at any age
Depends on Stage
Menopausal vs Premenopausal
Clinical trials have supported 5 years of aromatase inhibitor treatment for postmenopausal women with hormone receptor–positive, nonmetastatic breast cancer, but some oncologists continue treatment beyond 5 years. This practice finally was addressed in a large randomized trial: Women who had already completed 5 years of letrozole received either letrozole or placebo for 5 additional years. Five-year disease-free survival was significantly higher with letrozole than with placebo (95% vs. 91%), but overall 5-year survival was similar in the two groups. Because aromatase inhibitors do have adverse effects, discussions on whether to proceed with an additional 5 years of treatment (total, 10 years) should be informed by this trial (NEJM JW Gen Med Aug 1 2016 and N Engl J Med 2016; 375:209).
Bone Metastases
Bisphosphonate Therapy
Bone is the most common site of metastatic disease at initial presentation and at the time of breast cancer recurrence. Bone metastases are often detected with a bone scan obtained in the staging of locally advanced cases or obtained because of clinical suspicion in the previously treated patient. Confirmation with plain radiographs, MRI, and/or CT is frequently needed because nearly 10% of lytic lesions may not be detected with a nuclear medicine scan. These other radiographic studies also help to delineate the extent of the metastatic disease. After bone metastases are confirmed, bisphosphonate therapy has been shown to diminish pain and decrease the rate of skeletal events and complications related to the bone metastases.
Bisphosphonate therapy should be administered with other palliative systemic treatments such as hormonal manipulation or chemotherapy. It is typically given intravenously every 3–4 weeks and continued indefinitely even though long-term studies are lacking. Regular dental exams, laboratory monitoring, and creatinine and renal function, as well as evaluation of calcium and vitamin D levels, are also recommended due to the risk of osteonecrosis of the jaw, renal insufficiency, and hypocalcemia associated with prolonged therapy.
Control of Nausea
Olanzapine for prevention of nausea and vomiting induced by highly emetogenic chemotherapy regimens
For patients receiving cisplatin and other highly emetogenic chemotherapy regimens, we suggest the addition of olanzapine on days 1 through 4 to standard antiemetic therapy (a combination of a 5-HT3 receptor antagonist, dexamethasone, and an NK1R antagonist) (Grade 2B).
The antipsychotic olanzapine may be a particularly useful agent for preventing delayed chemotherapy-induced nausea and vomiting, which is often poorly controlled with conventional antiemetics. The effectiveness of adding olanzapine to a standard antiemetic regimen was shown in a trial in which 380 patients receiving highly emetogenic chemotherapy (cisplatin or doxorubicin/cyclophosphamide for breast cancer) were randomly assigned to dexamethasone, an NK1R antagonist, and a 5-HT3 receptor antagonist plus either olanzapine (10 mg daily orally on days 1 through 4) or placebo [4]. The proportion of patients with no chemotherapy-induced nausea (the primary endpoint) was higher with olanzapine both in the first 24 hours after chemotherapy and in the delayed period. Rates of complete response (no emesis and no use of rescue medication) were also higher with olanzapine over a five-day period. Patients receiving olanzapine had more sedation on day 2 (severe in 5 percent), which resolved despite continued olanzapine. On the basis of this trial, we now suggest the addition of olanzapine on days 1 through 4 to standard antiemetic therapy for patients receiving highly emetogenic chemotherapy. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults", section on 'Olanzapine'.)
Radiation Therapy
UMMC is the only center to offer the four leading radiation technologies designed to protect the heart. They include:
- AlignRT with Deep Inspiration Breath Hold: The ideal time to deliver radiation to the left breast is when a patient takes a deep breath, which moves the heart posteriorly and inferiorly away from the chest wall. AlignRT helps radiation therapists know when patients are in this optimal position; it also allows the therapist to stop the radiation beam when the patient breathes. This technology brings down the amount of radiation reaching the heart to virtually nil and has been part of UMMC’s radiation treatment arsenal for about five years.
- Proton therapy: Compared to traditional photon radiation, proton therapy beams are more precise because they can be programmed to stop at the treatment site without penetrating deeper. Using this option in certain breast cancer patients — depending on tumor location and shape, as well as lymph node involvement — can reduce radiation exposure to the heart. The Maryland Proton Treatment Center, one of only about 20 such facilities in the country, opened in February 2016.
- Thermal therapy: By heating tumors growing on the chest wall up to 110 degrees, this technology enhances the efficacy of radiation therapy. UMMC is the only center in the region offering thermal therapy.
- GammaPod: The first device of its kind, this form of stereotactic radiation therapy was developed by UMMC faculty members. The machine is fully dedicated to treating early-stage breast cancer, and delivers a high dose of 36 focused radiation beams while patients are treated in a prone position, allowing the tumor to fall away from the chest wall. UMMC is currently conducting a preapproval trial on GammaPod for the Food and Drug Administration.{1}
Metastatic spread is often to lungs, liver, and bone.
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