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Breast cancer

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Updated 2024 ASCO guidelines for adjuvant cyclin-dependent kinase inhibitors in patients with early breast cancer.

Background

Overview

Definition
Breast cancer is a malignant tumor arising from breast cells. The two primary types of breast cancer include ductal carcinoma and lobular carcinoma, originating in the milk-transporting ducts and the milk-producing lobules, respectively. It is classified as either noninvasive (carcinoma in situ) or invasive (infiltrating). Invasive breast cancer is further categorized into early breast cancer, locally advanced breast cancer, and advanced/metastatic breast cancer. Based on the expression of hormone receptors and HER2, tumors are classified into three main groups: HR-positive (luminal tumors), HER2-positive, and the remaining subtypes being collectively referred to as triple-negative breast cancer (including basal-like and claudin-low tumors).
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Pathophysiology
High-penetrance genes BRCA1 and BRCA2 are associated with an increased predisposition to breast cancer. Mutations in these genes increase the risk of both breast and ovarian cancers. TP53 is another critical gene associated with breast cancer risk, often correlated with more aggressive disease and poor prognosis. Additionally, several single nucleotide polymorphisms, including FGFR2, TNRC9, MAP3K1, LSP1, and CASP8, have been identified as associated with an increased risk of breast cancer.
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Epidemiology
Breast cancer is the most common cancer worldwide, both in women and overall, with an estimated incidence rate of 119.2 per 100,000 woman-years in the US.
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Risk factors
Risk factors for breast cancer include age, family history of breast or ovarian cancer, genetic mutations such as BRCA1 or BRCA2, history of breast atypical hyperplasia and carcinoma in situ, increased mammographic density, prior radiation exposure, and certain lifestyle factors such as alcohol consumption, obesity, and lack of physical activity.
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Disease course
Clinically, breast cancer may present with a palpable breast mass, nipple discharge, skin changes such as erythema, peau d'orange, and ulceration, and asymmetric thickening or nodularity. Focal breast pain and axillary mass may also be present.
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Prognosis and risk of recurrence
The prognosis of breast cancer is influenced by the stage at diagnosis, with early-stage cancers generally having a better prognosis than late-stage cancers. The specific molecular characteristics of the tumor, such as hormone receptor status and HER2 status, also play a significant role in determining prognosis. Basal-like breast cancer, which is often triple-negative, is associated with a poor prognosis. The 5-year age-adjusted breast cancer mortality rate in the US is estimated at 19.6 per 100,000 female-years.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of breast cancer are prepared by our editorial team based on guidelines from the American Society for Radiation Oncology (ASTRO 2024,2018), the American Society of Clinical Oncology (ASCO 2024,2023,2022,2021,2020,2019,2018,2017), the European Society of Medical Oncology (ESMO 2024,2021), the Society of Surgical Oncology (SSO/ASCO 2024), the U.S. Preventive Services Task Force (USPSTF ...
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Screening and diagnosis

Indications for screening, average-risk females
As per ESMO 2024 guidelines:
Obtain regular (every 2 years) mammography in average-risk females aged 50-69 years.
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Consider obtaining regular mammography in females aged 40-49 and 70-74 years, although there is less evidence of benefit.
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  • Indications for screening (high-risk females)

Diagnostic investigations

History and physical examination: as per ESMO 2024 guidelines, elicit complete medical and family history, including menopausal status (measure serum estradiol and FSH levels if in doubt).
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  • Breast imaging

  • Imaging for staging (early breast cancer)

  • Imaging for staging (metastatic breast cancer)

  • Laboratory tests

  • Assessment of fracture risk

Diagnostic procedures

Biopsy and histopathology, early breast cancer: as per ESMO 2024 guidelines, obtain pretreatment pathological assessment, including a complete histomorphological, immunohistochemical, and molecular assessment, if applicable, at the time of diagnosis, with primary tumor histology and axillary node histology/cytology (if node involvement is suspected clinically).
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  • Biomarker testing, early breast cancer (general principles)

  • Biomarker testing, early breast cancer (Oncotype)

  • Biomarker testing, early breast cancer (MammaPrint)

  • Biomarker testing, early breast cancer (EndoPredict)

  • Biomarker testing, early breast cancer (Prosigna)

  • Biomarker testing, early breast cancer (Ki67)

  • Biomarker testing, early breast cancer (IHC4)

  • Biomarker testing, early breast cancer (BCI)

  • Biomarker testing, early breast cancer (CTS5)

  • Biomarker testing, early breast cancer (tumor infiltrating lymphocytes)

  • Biomarker testing, early breast cancer (PD-L1)

  • Biomarker testing, early breast cancer (circulating tumor cells)

  • Biomarker testing, early breast cancer (ctDNA)

  • Biomarker testing, metastatic breast cancer (NTRK fusion)

  • Biomarker testing, metastatic breast cancer (PD-L1)

  • Biomarker testing, metastatic breast cancer (dMMR/MSI-H)

  • Biomarker testing, metastatic breast cancer (tumor mutational burden)

  • Biomarker testing, metastatic breast cancer (TROP2)

  • Biomarker testing, metastatic breast cancer (homologous recombination deficiency)

  • Biomarker testing, metastatic breast cancer (circulating tumor cells)

  • Biomarker testing, metastatic breast cancer (ctDNA)

  • Genetic testing (BRCA1/2)

  • Genetic testing (ESR1)

  • Genetic testing (PIK3CA)

  • Genetic testing (PALB2)

  • Genetic testing (other genes)

Medical management

General principles: as per ESMO 2024 guidelines, manage patients in specialized breast units/centers where available by a specialized multidisciplinary team that can refer patients to other specialties.
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  • Management of DCIS (breast-conserving surgery)

  • Management of DCIS (whole-breast irradiation)

  • Management of DCIS (partial-breast irradiation)

  • Management of DCIS (adjuvant endocrine therapy)

  • Management of early breast cancer (neoadjuvant therapy, general principles)

  • Management of early breast cancer (neoadjuvant therapy, HR+ HER2-)

  • Management of early breast cancer (neoadjuvant therapy, HER2+)

  • Management of early breast cancer (neoadjuvant therapy, triple-negative)

  • Management of early breast cancer (neoadjuvant therapy, monitoring)

  • Management of early breast cancer (breast-conserving surgery)

  • Management of early breast cancer (mastectomy)

  • Management of early breast cancer (sentinel lymph node biopsy)

  • Management of early breast cancer (axillary lymph node dissection)

  • Management of early breast cancer (locoregional lymph node irradiation)

  • Management of early breast cancer (ultrasound-guided staging)

  • Management of early breast cancer (adjuvant radiotherapy, after breast-conserving surgery)

  • Management of early breast cancer (adjuvant radiotherapy, after mastectomy)

  • Management of early breast cancer (adjuvant endocrine therapy, HR+ HER2-)

  • Management of early breast cancer (adjuvant CDK and PARP inhibitors, HR+ HER2-)

  • Management of early breast cancer (adjuvant chemotherapy, HR+ HER2-)

  • Management of early breast cancer (adjuvant chemotherapy, HR+, HER2-)

  • Management of early breast cancer (adjuvant systemic therapy, HER2+)

  • Management of early breast cancer (adjuvant systemic therapy, triple-negative)

  • Management of early breast cancer (ovarian suppression)

  • Management of early breast cancer (bone-modifying agents)

  • Management of metastatic breast cancer (systemic therapy, first-line, HR+ HER2-)

  • Management of metastatic breast cancer (systemic therapy, second-line, HR+ HER2-)

  • Management of metastatic breast cancer (systemic therapy, third-line, HR+ HER2-)

  • Management of metastatic breast cancer (systemic therapy, first-line, HER2+)

  • Management of metastatic breast cancer (systemic therapy, second-line, HER2+)

  • Management of metastatic breast cancer (systemic therapy, third-line, HER2+)

  • Management of metastatic breast cancer (systemic therapy, triple-negative)

  • Management of metastatic breast cancer (ovarian suppression)

  • Management of metastatic breast cancer (bone-modifying agents)

  • Management of metastatic breast cancer (local management)

  • Management of metastatic breast cancer (management of bone metastases)

  • Management of metastatic breast cancer (management of brain metastases)

Nonpharmacologic interventions

Lifestyle modifications: as per ESMO 2024 guidelines, encourage adopting a healthy lifestyle, including exercising regularly, avoiding being overweight, and minimizing alcohol intake.
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Specific circumstances

Patients in menopause: as per SOGC 2021 guidelines, optimize modifiable risk factors, such as weight, smoking, alcohol use, and exercise, in menopausal patients considering hormone therapy.
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  • Elderly patients

  • Male patients (genetic testing)

  • Male patients (management of early breast cancer)

  • Male patients (management of metastatic breast cancer)

  • Male patients (surveillance)

Patient education

General counseling
As per ESMO 2024 guidelines:
Provide information on diagnosis and treatment choices repeatedly (both verbally and in writing) in a comprehensive and easily understandable manner. Provide reliable patient-centered websites or similar sources of information.
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Ensure that patients are actively involved in all management decisions and have equitable access to the full range of reproductive care options, including pregnancy counseling, contraception, and fertility preservation. Discuss fertility and fertility preservation with younger premenopausal patients (irrespective of stage of disease) before initiating any systemic treatment.
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  • Reproductive counseling

Preventative measures

Chemoprophylaxis
As per USPSTF 2019 guidelines:
Offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, in females at increased risk for breast cancer and at low risk for adverse medication effects.
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Do not offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, in females not at increased risk for breast cancer.
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Follow-up and surveillance

Monitoring for medication adverse effects: as per ESMO 2024 guidelines, obtain regular bone density evaluation in patients on aromatase inhibitors or undergoing ovarian function suppression.
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  • Assessment of treatment response

  • Surveillance for metastases

  • Surveillance for recurrence (general principles)

  • Surveillance for recurrence (early breast cancer)

  • Surveillance for other malignancies

  • Long-term survivorship