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Health Protocols

Breast Cancer

Diagnosis

After a suspicious lesion is detected by mammogram or MRI, the medical team must do further tests to diagnose the condition. The follow-up tests often begin with additional imaging. A diagnostic mammogram is a more extensive version of the screening mammogram (Jensen 2010). For some women, an MRI or ultrasound, after abnormal mammography findings, may be helpful (He 2017; Flobbe 2003; Bickelhaupt 2017). An ultrasound uses sound waves to image the area of the breast that looked suspicious on the mammogram (Guo 2017).

Biopsy

After additional imaging, a biopsy is taken so a pathologist can examine some tissue in the suspicious area (John 2016). Most biopsy procedures use a thin needle to remove a piece of tissue (White 2001; Wang, He 2017). Ultrasound, MRI, and X-rays can all be used to guide the placement of the needle depending on the appearance and location of the suspicious area (Chevrier 2016; Klimberg 2016; Omofoye 2017; PDQ Screening Prevention Editorial Board 2017b). Occasionally, a surgical procedure is required to biopsy an area that cannot be reached with a needle (Anonymous 2016).

If cancer is detected in the biopsy, the pathologist will determine the subtype—for instance, ductal or lobular (PDQ Screening Prevention Editorial Board 2017b; Greeley 1997). The tumor is assigned a histological grade that indicates whether the cancer cells still look close to normal (grade 1), have characteristics of both normal and abnormal cells (grade 2), or are quite abnormal and fast-growing (grade 3) (Knuttel 2016; Zhang, Cao 2012). Lastly, the pathologist will assess the molecular characteristics of the cells: first, whether the tumor cells have estrogen and progesterone receptors, and second whether they are overexpressing HER2 (Hammond 2010; Nofech-Mozes 2012). Triple negative breast cancers do not have estrogen receptors, progesterone receptors, or HER2 overexpression (Saraiva 2017). Determining whether the cancer cells express these receptors is important in treatment planning, as some therapies target these receptor pathways.

Prognosis and Staging

After diagnosis, doctors must assess how big the primary tumor is and whether it has spread. This information is described in the cancer stage (Table 2) (Davidson 2016; PDQ Adult Treatment Editorial Board 2017).

Table 2: Breast Cancer Stages

Stage Definition

Stage 0

Non-invasive conditions (DCIS, LCIS, or Paget disease of the nipple)

Stage I

Very small tumors (<2 cm) with either no affected lymph nodes or just a small cluster of cancer cells in one lymph node

Stage II

A large tumor (>5 cm) with no affected lymph nodes or a smaller tumor (2‒5 cm) with 1‒3 affected lymph nodes in the armpit or near the breastbone

Stage III

A large tumor (>5 cm) with a small cluster of cancer cells in one lymph node or any size tumor with many affected lymph nodes

Stage IV

Cancer that has spread to other organs of the body

Blood tests may indicate whether the liver or the bones are being affected by a metastasis (NCCN 2016). If the results are abnormal or if the patient is experiencing pain or any other symptom, the doctor may use a bone scan to check the bones or a computed tomography (CT) scan, MRI, or ultrasound to check the abdomen, chest, or pelvic area (NCCN 2017b).

Newer Molecular and Genetic Tests

Breast cancer stage, hormone receptor status, and cancer subtype can provide information on a patient’s prognosis that can guide treatment decisions. New molecular tests have been developed that provide additional information (Nicolini 2017; Gyorffy 2015). The MammaPrint test is approved by the Food and Drug Administration (FDA) for women with stage I or II breast cancer (Gyorffy 2015). This test examines the expression levels of 70 genes in the tumor (Drukker 2013) and divides women into high-risk and low-risk categories (Viale 2017). Patients in the high-risk category may need chemotherapy after surgery (Drukker 2013; Knauer 2010).

Similarly, the Oncotype DX test examines 21 genes and divides patients into low-risk, intermediate-risk, and high-risk groups (Nicolini 2017). The test can help determine who should have chemotherapy after surgery (Bear 2017; Stemmer 2017). Recently published studies have found that the test is underutilized, particularly among older, poor, or black patients (Kozick 2017; Ricks-Santi 2017). Researchers are investigating how to make this test more universally available (Roberts 2016). Future trials will directly compare the Mammaprint and Oncotype Dx tests along with several newer tests described in the “Novel and Emerging Strategies” section.

Table 3: Molecular Tests for Breast Cancer Prognosis

Test name

Patient population

Result

Clinical application

FDA approval

Selected clinical data

Oncotype Dx

Stage I, II, IIIa
ER positive
HER2 negative
Lymph node negative or positive (1–3 nodes)

Provides a breast cancer recurrence score ranging from 0 to 100

Predicts how likely cancer is to return within 10 years

No

Among patients taking tamoxifen, 3.2% of those with a low-risk score had disease recurrence within 10 years and 39.5% of those with a high-risk score had a recurrence. When a similar group of patients with a high-risk score were treated with chemotherapy along with tamoxifen, only 11.9% had a recurrence (Paik 2006).

Breast Cancer Index Test

Stage I, II, IIIa
ER positive
Endocrine therapy
HER2 negative
Lymph node negative or positive (1–3 nodes)

Classifies patients into low-, intermediate-, and high-risk categories

Predicts how likely cancer is to return late (after five years) and overall (within 10 years)

No

Among patients with positive lymph nodes, 13.4% of those with a high risk score and 3.5% of those with a low risk score had a disease recurrence between five and 10 years after treatment (Sgroi 2013).

Prosigna

Stage I or II
Postmenopausal
ER positive
Endocrine therapy
Lymph node negative or positive (1–3 nodes)

Classifies patients into low, intermediate, and high risk of recurrence

Predicts how likely cancer is to return within 10 years

Yes

Among patients with negative lymph nodes, only 3.5% in the low risk of recurrence group had a disease recurrence within 10 years without any chemotherapy (Gnant 2014).

Endopredict

Stage I, II
ER positive
HER2 negative
Lymph node negative or positive (1–3 nodes)

Molecular score is combined with tumor stage and nodal status to create a risk score ranging from 1 to 6

Predicts how likely cancer is to return within 10 years

No

After 10 years of follow up of breast cancer patients treated with endocrine therapy, 1.8% in the low-risk group and 12.3% in the high-risk group had cancer recurrences (Dubsky 2013).

Mammaprint

Stage I or II
ER positive or negative
HER2 positive or negative
Lymph node negative or positive (1–3 nodes)

Classifies patients into low-risk, high-risk, and borderline categories

Predicts how likely cancer is to return within five years

Yes

Among patients with some high-risk clinical features (eg positive lymph nodes, large tumors) but low Mammaprint risk score, the benefit of chemotherapy was limited: 94.7% were disease free after five years without chemotherapy and 96.2% with chemotherapy (Cardoso 2016).

 

Genetic Testing for BRCA1 and BRCA2 Mutations

BRCA1 and BRCA2 are genes that code for proteins that normally suppress tumors. The proteins normally repair damaged DNA and maintain genetic stability (Toland 2017). When either BRCA1 or BRCA2 are not functioning correctly, the resulting cellular abnormalities increase the risk of breast and ovarian cancer, and that of some other cancers (Davidson 2016; Mehrgou 2016; Scully 2000). Mutations in BRCA1 or BRCA2 can be inherited from either parent.

BRCA1 and BRCA2 mutations that can be passed to offspring play a role in only about 30% of heritable breast cancers (Valencia 2017). As DNA analysis technologies have advanced, more genes can be analyzed to try to identify the contribution of other mutations (Afghahi 2017; Prapa 2017). For instance, for women under 40, inherited changes in a protein that interacts with BRCA2, called PALB2, can increase the risk of breast cancer nine-fold over the average risk (Antoniou 2014; Erel 2014).

Women should consider genetic testing if their family history is suggestive of an increased risk of breast or ovarian cancer (Davidson 2016; Cropper 2017; Moyer 2014). BRCA1 and BRCA2 mutations are more common in people with Ashkenazi Jewish ancestry, women who have cancer in both breasts, or when both ovarian and breast cancer are present in the same woman or the same family (Manchanda 2017; NCI 2018). People considering genetic testing should talk with a genetic counselor before and after testing (NCI 2018; Petrucelli 2016).

Awareness of mutations can help optimize treatment plans (Paterson 2017). Women who test positive for a mutation should be screened for cancer more carefully. Some experts recommend that clinical breast exams and mammograms begin between age 25 and 35 for women with known mutations (NCI 2018; Llort 2015). MRI beginning at age 25 may also improve the chance of detecting cancers early (Llort 2015; Petrucelli 2016). To reduce the risk of developing cancer, some women with mutations choose to have their breasts and/or ovaries surgically removed (Petrucelli 2016; NCI 2018; Llort 2015; Eisemann 2018).