Breast cancer treatment guidelines 2025

Breast cancer is the most common cancer in Thai women and a major problem worldwide. With a continuously increasing incidence, it is important to understand modern treatment guidelines based on leading international organizations such as the National Comprehensive Cancer Network (NCCN) , the American Society of Clinical Oncology (ASCO) , and the European Society for Medical Oncology (ESMO) to ensure appropriate patient care and the best treatment outcomes.

Current approaches to breast cancer treatment are moving towards “personalized medicine”, taking into account many factors such as the stage of the disease, the molecular characteristics of the cancer cells, the overall health of the patient, as well as the individual needs and circumstances, in order to achieve the most effective treatment with the least side effects. ESMO also emphasizes the importance of shared decision-making between the medical team and the patient in planning treatment.

Over the past decade, medical science in cancer treatment has advanced rapidly, covering more accurate diagnosis, less invasive and breast-preserving surgical techniques, more targeted radiation therapy for cancer cells, and most importantly, the development of “drug therapy.” Understanding the molecular mechanisms of cancer cell formation and growth has led to the development of “targeted therapy” that acts specifically and “immunotherapy” that uses the body’s immune system to fight cancer.

This is a significant change. In the past, chemotherapy could affect normal cells. Today, medicine is focused on "Comprehensive Precision Cancer Treatment", which analyzes the characteristics of each patient's cancer to select the most appropriate treatment. NCCN and ESMO support the use of molecular information to make treatment decisions, whether it is targeted drugs or improving chemotherapy regimens to be more effective and develop drugs that reduce side effects and make treatment more tolerable. These advances not only increase survival rates but also significantly improve the quality of life for breast cancer patients.

Diagnosis and staging of breast cancer

Accurate breast cancer diagnosis and correct staging are crucial first steps in planning appropriate treatment, according to international guidelines.

Screening and diagnosis methods

Screening aims to detect cancer at an early stage, which increases the chance of successful treatment. Internationally recommended methods of breast cancer screening and diagnosis include:

• Breast Self-Examination (BSE): Although the scientific evidence is not clear that BSE directly reduces breast cancer mortality, regular breast self-examination can help women become familiar with their breasts and spot any abnormal changes early.

• Clinical Breast Examination (CBE): Palpation of the breast and lymph nodes in the armpit by a doctor or other qualified health care professional. It is recommended every 1-3 years, depending on age, and should be done in conjunction with a mammogram to increase diagnostic accuracy.

• Mammography: As the primary and most effective screening tool for breast cancer, ESMO 2024 recommends mammography as part of tumour assessment and recommends annual follow-up mammography after treatment.

• Breast ultrasound: Often used as an adjunct to mammography, especially in women with relatively dense breast tissue, or to assess the characteristics of lumps or abnormalities found. ESMO 2024 recommends breast ultrasound for the evaluation of tumors.

• Magnetic Resonance Imaging (MRI): NCCN 2024 recommends annual breast MRI for patients with a personal history of breast cancer and dense breast tissue or diagnosed at age 50 or younger. ESMO recommends MRI in select cases based on available indications.

• Biopsy: The most important and essential step in confirming a diagnosis of breast cancer. ASCO/CAP recommends core biopsy for diagnostic purposes and to screen for biomarkers. Similarly, ESMO 2024 recommends core biopsy to assess cell grade , estrogen receptor ( ER ), progesterone receptor ( PR ), HER2 , and Ki67. ESMO also recommends biopsy of metastatic lesions to confirm histological characteristics and reassess biomarkers.

  
  

Evaluation for metastatic disease is only recommended in patients with stage IIb or above (especially with multiple lymph node metastases), patients at high risk of recurrence, or patients with symptoms, according to the 2024 ESMO guidelines.

Genetic assessment using NCCN criteria found that patients with a high prevalence of genetic mutations had cancer at a younger age than 50 years, multiple breast cancers , first-degree relatives with breast or ovarian cancer or male breast cancer, and triple negative cancer, and also supported the use of multigene panel tests .

Breast Cancer Staging (TNM) System and Grading

After confirming the diagnosis of breast cancer, the next step is to assess the stage of the disease, which is very important in prognosis and treatment planning. The most widely used system is the TNM system of the AJCC (American Joint Committee on Cancer) :

• T (Tumor): refers to the size and spread of the breast cancer.

• N (Node): refers to the spread of cancer cells to nearby lymph nodes, especially the lymph nodes in the armpit.

• M (Metastasis): refers to the spread of cancer cells to distant organs such as bones, lungs, liver, or brain.

In addition to the TNM staging system , there is also an assessment of cancer cell grade , which is an assessment of the abnormal characteristics of cancer cells when viewed under a microscope, including the rate at which cancer cells divide. It is generally divided into 3 grades:

• Grade 1 (Low grade): Cancer cells resemble normal cells, divide slowly, and have a low tendency to spread.

• Grade 2 (Intermediate grade): The characteristics and divisions are between Grades 1 and 3.

• Grade 3 (High grade): Cancer cells are very abnormal, divide rapidly, and have a high tendency to spread.

Table 1: Summary of TNM Staging System for Breast Cancer (refer to AJCC Staging Manual).

factor	Subdivision	Brief description
T (Tumor)	This	Carcinoma in situ (stage 0 cancer)
	T1 (T1mi, T1a, T1b, T1c)	The tumor is no larger than 2 centimeters in size.
	T2	The tumor is larger than 2 centimeters but not more than 5 centimeters.
	T3	The tumor is larger than 5 centimeters.
	T4 (T4a, T4b, T4c, T4d)	The cancer has spread to the chest wall or skin, or is inflammatory breast cancer.
N (Node)	N0	No spread to nearby lymph nodes
	N1 (N1mi, N1a, N1b, N1c)	Cancer has spread to 1-3 lymph nodes in the same armpit, or cancer cells are found in the internal mammary nodes on SLNB examination.
	N2 (N2a, N2b)	The cancer has spread to 4-9 lymph nodes in the same armpit or has spread to lymph nodes within the breast as detected clinically.
	N3 (N3a, N3b, N3c)	Spread to wider lymph nodes, such as ≥ 10 axillary lymph nodes, subclavian lymph nodes, or supraclavicular lymph nodes.
M (Metastasis)	M0	There is no spread to distant organs.
	M1	It has spread to distant organs (eg, bones, lungs, liver, brain).

Note: This table is a preliminary summary only. Staging details are complex and should be assessed by a medical professional according to international guidelines such as the AJCC.

Molecular Subtypes of Breast Cancer

In addition to anatomical and cytological assessment, molecular subtype classification of breast cancer is currently very important in planning treatment, especially drug therapy. Biopsy will include examination of receptors on the cancer cell surface, including:

• Estrogen Receptor (ER):

  • ER-positive (ER+): Cancer cells have estrogen receptors.

  • ER-negative (ER-): Cancer cells lack estrogen receptors.

• Progesterone Receptor (PR):

  • PR-positive (PR+): Cancer cells have progesterone receptors.

  • PR-negative (PR-): Cancer cells lack progesterone receptors.

• Human Epidermal Growth Factor Receptor 2 (HER2/neu) receptor:

  • HER2-positive (HER2+): Cancer cells express more of the HER2 protein than normal.

  • HER2-negative (HER2-): Cancer cells express normal levels of the HER2 protein.

  • HER2-low: This group is becoming increasingly important, especially with certain antibody-drug conjugates. It refers to cancers with low HER2 expression (IHC 1+ or IHC 2+/ISH-).

  
  

  Breast cancer can be divided into major subtypes based on the expression of these receptors, which affects prognosis and different treatment approaches, including:

  
  

• Luminal A breast cancer:

  • Molecular characteristics: Estrogen receptor positive (ER+), may or may not be progesterone receptor positive (PR+/-), and HER2-negative with low Ki-67 values (indicating slow cancer cell division rate).

  • Disease behavior: Generally considered the best prognosis type, with slow growth and good response to hormone therapy.

  • Treatment approach: Focuses on hormonal therapy. Chemotherapy may be considered in some high-risk cases.

• Luminal B breast cancer:

  • Molecular characteristics: estrogen receptor positive (ER+), may or may not have progesterone receptor positive (PR+/-), and high Ki-67 (indicating faster rate of cancer cell division), or sometimes HER2-positive (called Luminal B, HER2-positive) or Triple Positive.

  • Disease behavior: More severe than Luminal A, higher chance of recurrence or spread.

  • Treatment approach: Often requires a combination of hormonal therapy and often chemotherapy, especially in those with high Ki-67. In the case of HER2-positive, HER2-targeted drugs may also be used.

• HER2-positive breast cancer:

  • Molecular characteristics: Cancer cells overexpress HER2 protein ( HER2 + ), and often lack hormone receptors (ER- and PR-).

  • Disease behavior: It is a type that has grown and spreads quite rapidly in the past, but currently the prognosis is much better with HER2-targeted drugs.

  • Treatment approach: The mainstay of treatment is chemotherapy with HER2- targeted drugs (eg, Trastuzumab, Pertuzumab, various ADCs) in both early and metastatic disease.

• Triple-Negative Breast Cancer (TNBC):

  • Molecular characteristics: Cancer cells lack all three receptors: ER-negative, PR-negative, and HER2-negative.

  • Disease behavior: It is a relatively aggressive type, tends to grow and spread rapidly, and has a higher chance of recurrence than other types at the same stage of the disease. However, TNBC often responds well to chemotherapy in the early stages.

  • Treatment approaches: The mainstay of treatment is chemotherapy, but immunotherapy and some targeted drugs such as PARP inhibitors (in patients with BRCA gene mutations) are currently being used. In the future, there will be more research into antibody-drug conjugates (ADCs) that are more specific for TNBC.

    
    

This molecular subtyping is at the heart of personalized medicine in breast cancer, as it determines whether a patient will respond to hormonal therapy (for HR+) or HER2-targeted therapy ( for HER2+ ). For TNBC , the mainstay of treatment is chemotherapy, but newer immunotherapies and targeted agents are now being developed. In addition, measurement of Ki-67 levels , an indicator of tumor cell proliferation rate, is another prognostic factor and the need for chemotherapy, especially in hormone receptor-positive cancers. ESMO and NCCN recommend using this information to make treatment decisions.

Mainstream treatment approaches for breast cancer

Current breast cancer treatment is a multimodal therapy that uses a combination of different treatment methods to achieve the best results.

Surgery

Surgery is the mainstay of treatment, especially in early-stage breast cancer. The main surgical modalities according to international guidelines include:

• Breast-Conserving Surgery (BCS) or Lumpectomy: This is a surgical procedure that removes the cancer and some of the normal tissue around it, while preserving most of the breast. It is usually done on women with stage 0 to stage 2 breast cancer, or in some cases, stage 3 breast cancer. Women who have breast-conserving surgery will always need to receive radiation therapy to the breast area.

• Mastectomy: This is a surgical procedure that removes all of the breast tissue, including the skin and nipple.

• Lymph Node Surgery:

  • Sentinel Lymph Node Biopsy (SLNB): Helps assess the spread of cancer to lymph nodes and avoid unnecessary removal of entire lymph nodes.

  • Axillary Lymph Node Dissection (ALND): Performed if there is spread to the sentinel lymph nodes or other indications.

• Breast reconstruction surgery (Breast Reconstruction): Can be done at the same time as or after cancer surgery.

The decision to undergo surgery must be made jointly by the doctor and the patient, taking into account factors such as the size and location of the cancer, breast characteristics, and the patient's needs.

Radiotherapy

Radiation therapy is a local treatment that uses high-energy rays to destroy cancer cells.

• Indications for radiotherapy:

  • After breast conserving surgery: the standard to reduce recurrence

  • After a total mastectomy: May be considered in high-risk cases, such as large tumors or lymph node metastases. The NCCN recommends radiation to the chest wall and the entire mastectomy area.

  • Palliative care: to relieve symptoms from spreading

• Radiation Techniques: Modern techniques such as IMRT or 4D Radiotherapy or Intraoperative Radiation Therapy (IORT) allow for more precise radiation delivery and less impact on nearby organs.

• Side effects: Acute (e.g. dermatitis, fatigue) and long-term (e.g. hardening of the tissues, effects on the lungs or heart) side effects may occur.

  
  

Systemic Therapy

Systemic therapy plays an important role in eradicating any remaining cancer cells or controlling the disease if it has spread.

• Chemotherapy:

  • Principle: Use drugs to destroy cancer cells.

  • Indications and purposes:

    • Preoperative chemotherapy (Neoadjuvant chemotherapy): To shrink the tumor or assess response to therapy, ASCO/ESMO recommends it in patients with inflammatory breast cancer or in whom response to therapy may alter treatment options.

    • Postoperative chemotherapy (adjuvant chemotherapy): to reduce the risk of recurrence

    • Palliative Chemotherapy: To control the disease and relieve symptoms.

  • Commonly used regimens: Anthracyclines and taxanes are the mainstays. ASCO/ESMO recommends regimens containing anthracyclines and taxanes for TNBC patients with positive lymph nodes or T1c or greater tumors. Carboplatin may be considered in addition in TNBC patients to increase the pathological complete response ( pCR ) rate.

  • Chemotherapy considerations: Based on disease stage, grade, receptor status, Ki-67, genetic signature testing (eg, Oncotype DX ) may aid decision-making for early-stage HR+/HER2- patients, as per NCCN and ESMO guidelines.

  • Side effects: Nausea, vomiting, hair loss, fatigue, low immunity

    
    

• Hormone Therapy (Hormone Therapy or Endocrine Therapy):

  • Principle: For HR-positive (ER+ and/or PR+) cancers.

  • Commonly used drugs:

    • Tamoxifen: Can be used both before and after menopause.

    • Aromatase Inhibitors (AIs): Such as Letrozole, Anastrozole, Exemestane are used in postmenopausal women. NCCN recommends AIs for postmenopausal women.

    • GnRH Analogue (Ovarian Function Suppression - OFS): eg. Goserelin, Leuprolide used in premenopausal women in combination with Tamoxifen or AIs. NCCN recommends OFS for high-risk premenopausal patients with hormone-responsive tumors.

  • Duration of treatment: Generally 5-10 years.

    
    

• Targeted Therapy:

  • Principle: Drugs that act specifically on genetic or protein changes in cancer cells.

  • Drugs for HER2-positive breast cancer:

    • Trastuzumab (Herceptin): Often given in combination with chemotherapy.

    • Pertuzumab (Perjeta): Used in combination with trastuzumab and chemotherapy.

    • Antibody-Drug Conjugates (ADCs): Such as Ado-trastuzumab emtansine (T-DM1, Kadcyla) and Fam-trastuzumab deruxtecan (Enhertu). Enhertu is also effective in HER2-low.

    • Tyrosine Kinase Inhibitors (TKIs): e.g. Lapatinib, Neratinib, Tucatinib

  • CDK4/6 Inhibitors: e.g. Palbociclib, Ribociclib, Abemaciclib for HR+/HER2- metastatic disease in combination with antihormonal agents. NCCN recognizes Ribociclib as Category 1 preferred for adjuvant therapy for high-risk early-stage HR+/HER2- and as Category 1 preferred for first-line metastatic disease in combination with AI. ESMO and ASCO also have guidelines supporting the use of CDK4/6 inhibitors.

  • PARP Inhibitors: e.g. Olaparib, Talazoparib For patients with BRCA1/BRCA2 gene mutations, ASCO and ESMO recommend Olaparib as an adjuvant therapy in patients with gBRCA-mutated, HER2-negative, high-risk early breast cancer (OlympiA trial).

  • PI3K Inhibitors: eg. Alpelisib for HR+/HER2- metastatic with PIK3CA gene mutations in combination with Fulvestrant.

  • Side effects: Varies depending on the drug. May cause skin reactions, diarrhea, fatigue.

    
    

• Immunotherapy:

  • Principle: Stimulate the body's immune system to destroy cancer cells.

  • PD-1/PD-L1 Inhibitors: eg. Pembrolizumab, Atezolizumab

  • Indications in breast cancer: There is a role in advanced or metastatic TNBC with PD-L1 expression in combination with chemotherapy. ASCO recommends the addition of immune checkpoint inhibitors to chemotherapy as first-line treatment for patients with PD-L1 positive metastatic TNBC . ESMO has similar recommendations.

  • Side effects: Immune-related adverse events ( irAEs ) may occur in various organs.

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Table 2: Overview of main treatment modalities and primary indications (referring to NCCN, ASCO, ESMO).

Treatment Modality	Brief working principle	Primary Indications/Responsive Cancer Types	Examples of Drugs/Techniques
Surgery	Removal of the cancerous mass and associated lymph nodes	Early stage to locally advanced cancer (local disease control)	Lumpectomy, Mastectomy, SLNB, ALND
Radiotherapy	Use high-energy radiation to destroy cancer cells.	Post-breast conservation surgery augmentation, post-mastectomy augmentation in high-risk cases, symptomatic relief in metastatic cases	External Beam Radiotherapy (EBRT), IMRT
Chemotherapy	Use drugs to destroy rapidly dividing cancer cells.	Pre/post surgery in early to locally advanced, metastatic (multiple subtypes)	Anthracyclines (Doxorubicin), Taxanes (Paclitaxel), Carboplatin (for TNBC)
Hormone Therapy	Inhibit the effects of hormones on cancer cells or reduce hormone levels.	HR-positive cancer (ER+ and/or PR+)	Tamoxifen, Aromatase Inhibitors (Letrozole, Anastrozole), OFS (Goserelin)
HER2-Targeted Therapy	Inhibits the HER2 protein that stimulates the growth of cancer cells.	HER2-positive, HER2-low cancer (for some drugs)	Trastuzumab, Pertuzumab, T-DM1, Fam-trastuzumab deruxtecan, Lapatinib
Other Targeted Therapies	Acts specifically on genetic/other protein changes	HR+/HER2- metastatic (CDK4/6 inh.), BRCA-mutated (PARP inh.), PIK3CA-mutated (PI3K inh.)	Palbociclib, Ribociclib, Abemaciclib, Olaparib, Talazoparib, Alpelisib
Immunotherapy	Stimulate the immune system to destroy cancer cells.	Metastatic/advanced TNBC (PD-L1 positive)	Pembrolizumab, Atezolizumab

Treatment guidelines according to breast cancer stage

Treatment planning varies depending on the stage of the disease, as per NCCN, ASCO , and ESMO guidelines.

• Stage 0 breast cancer (Ductal Carcinoma In Situ - DCIS):

  • The main treatment is surgery (lumpectomy or mastectomy).

  • If breast-conserving surgery is performed followed by radiation therapy

  • Tamoxifen may be considered (if ER-positive).

• Early stage breast cancer (Stage I, II):

  • The goal is to cure the disease completely.

  • Surgery: BCS with RT or Mastectomy

  • Adjuvant Therapy:

    • Radiation therapy: Necessary after BCS, may be given after mastectomy in high-risk patients.

    • Chemotherapy: Consider risk (e.g. TNBC, HER2+, HR+ high risk)

    • Hormonal therapy: For HR-positive for 5-10 years, may be combined with a CDK4/6 inhibitor (eg, Ribociclib, Abemaciclib) in high-risk groups.

    • HER2-targeted therapy: for HER2-positive (eg, Trastuzumab +/- Pertuzumab) in combination with chemotherapy.

    • PARP inhibitor (Olaparib): for gBRCA-mutated, HER2-negative, high-risk EBC after chemotherapy.

  • Preoperative neoadjuvant therapy: may be considered to reduce tumor size or in aggressive (HER2+, TNBC) groups.

• Locally Advanced Breast Cancer (Stage III - Locally Advanced):

  • Usually starts with Neoadjuvant Systemic Therapy (chemotherapy +/- HER2-targeted drugs +/- immunotherapy in some cases of TNBC).

  • Followed by surgery (usually Mastectomy + ALND).

  • After surgery, most patients will receive radiation therapy.

  • Followed by continuous adjuvant treatment according to subtype

• Metastatic Breast Cancer (Stage IV - Metastatic):

  • The goal is to control the disease, relieve symptoms and maintain quality of life.

  • The mainstay of treatment is systemic therapy. The choice of drugs depends on the subtype, treatment history, patient condition, and metastatic site. ESMO recommends biopsy of the metastatic site for confirmation and reassessment of biomarkers.

    • HR-positive, HER2-negative: Hormonal therapy +/- CDK4/6 inhibitors is first-line therapy. Alpelisib may be used if PIK3CA mutation is present. PARP inhibitor may be used if BRCA mutation is present. Chemotherapy if hormone-resistant or disease is rapidly progressing.

    • HER2-positive: HER2-targeted drugs (eg, Trastuzumab + Pertuzumab + chemotherapy). If disease progresses, ADCs (T-DM1, Enhertu) or TKIs may be used.

    • HER2-low: Trastuzumab deruxtecan (Enhertu) is an important option after at least one course of chemotherapy and if HR+ and hormone-resistant.

    • Triple-Negative (TNBC): Chemotherapy is the mainstay. If PD-L1 positive, immunotherapy may be given in combination with chemotherapy. If BRCA mutated, PARP inhibitors. Sacituzumab govitecan is an option after prior treatment.

  • Radiation therapy or surgery may be used to control local symptoms.

  • Bone stabilizers (Bisphosphonates, Denosumab) for patients with bone metastases

Table 3: Summary of treatment guidelines by disease stage (referring to NCCN, ASCO, ESMO)

Stage of Disease	Brief description	Main treatment approaches	Treatment goals
Stage 0 (DCIS)	The cancer cells are in the milk ducts and have not spread.	Surgery (breast conservation + radiation or total breast removal) +/- Tamoxifen (if ER+)	Cure completely
Stage I-II (Early Stage)	Lump confined to breast +/- minor lymph nodes	Surgery + Radiation (if breast-conserving) + Adjuvant therapy according to subtype (hormonal +/- CDK4/6i, chemo, HER2-targeted, PARP inh.) +/- Neoadjuvant	Cure completely
Stage III (Locally Advanced)	Large lump/invasion of skin/chest wall/extensive lymph nodes	Neoadjuvant Systemic Therapy followed by Surgery and Radiotherapy + Adjuvant Therapy	Curable (less likely) or long-term control of the disease
Stage IV (Metastatic)	Cancer has spread to other organs.	Systemic Therapy (hormonal, chemotherapy, targeted, immunotherapy according to subtype and treatment sequence) +/- radiation/surgery for symptomatic relief +/- bone tonics	Control disease, relieve symptoms, and extend the quality of life of patients.

Specific treatment approaches for breast cancer subtypes

Selection of systemic therapy is mainly based on molecular subtype as per NCCN, ASCO, ESMO guidelines.

• Hormone receptor-positive and HER2-negative breast cancer (HR-positive, HER2-negative):

  • Early stage: The mainstay of treatment is hormonal therapy for 5-10 years, possibly in combination with a CDK4/6 inhibitor (Abemaciclib or Ribociclib) for 2-3 years in those at high risk of relapse (eg, positive lymph nodes, high grade, high Ki-67). Adjuvant chemotherapy is considered depending on risk factors or genetic signature test results.

  • In metastatic disease: Hormonal therapy with CDK4/6 inhibitors is the standard of care first. Alpelisib plus Fulvestrant may be used if there is a PIK3CA mutation. A PARP inhibitor may be used if there is a BRCA mutation . Chemotherapy if hormone-resistant or if the disease is rapidly progressing. Sacituzumab govitecan may be an option after ET resistance and at least two courses of chemotherapy.

• HER2-positive breast cancer:

  • In the beginning: HER2-targeted chemotherapy (Trastuzumab +/- Pertuzumab) plus chemotherapy for 1 year; if HR+, add on anti-hormonal agents.

  • In metastatic disease: First-line treatment is Trastuzumab + Pertuzumab + chemotherapy. If disease progresses, ADCs such as Ado-trastuzumab emtansine (T-DM1) or Fam-trastuzumab deruxtecan (Enhertu) or TKIs may be used.

• HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-):

  • In the spreading phase: Fam-trastuzumab deruxtecan (Enhertu) is an important option after at least one course of chemotherapy and in HR+ and hormone-resistant breast cancer, according to the internationally accepted DESTINY-Breast04 and DESTINY-Breast06 trials.

• Triple-negative breast cancer (TNBC):

  • In the beginning: Chemotherapy is the mainstay. Pembrolizumab may be considered in combination with chemotherapy (both neoadjuvant and adjuvant) in high-risk patients. If there is a BRCA mutation, Olaparib may be considered after completion of standard treatment (OlympiA trial).

  • In the spreading phase: Chemotherapy is the mainstay. If PD-L1 positive , immunotherapy (Pembrolizumab or Atezolizumab) is given in combination with chemotherapy. If BRCA mutated, PARP inhibitors are given . Sacituzumab govitecan is an option after prior treatment.

Table 4: Important targeted drugs and immunotherapies for different subtypes (referring to NCCN, ASCO, ESMO).

Cancer subtypes	Drug Class	Example Drugs	Key Indication/Condition
HR+/HER2-	CDK4/6 Inhibitors	Palbociclib, Ribociclib, Abemaciclib	Adjuvant (high-risk EBC), Metastatic (with ET)
	PI3K Inhibitors	Alpelisib	Metastatic (PIK3CA mutated, with Fulvestrant)
	PARP Inhibitors	Olaparib, Talazoparib	Adjuvant (gBRCAm, high-risk EBC), Metastatic (gBRCAm)
HER2+	Anti-HER2 mAbs	Trastuzumab, Pertuzumab	Early (adjuvant), Metastatic
	Anti-HER2 ADCs	Ado-trastuzumab emtansine (T-DM1), Fam-trastuzumab deruxtecan (Enhertu)	Metastatic (after receiving other medications)
	HER2 TKIs	Lapatinib, Neratinib, Tucatinib	Metastatic (after receiving other medications)
HER2-low	Anti-HER2 ADCs	Fam-trastuzumab deruxtecan (Enhertu)	Metastatic (after receiving chemotherapy, HR+ must be resistant to ET)
TNBC	PARP Inhibitors	Olaparib, Talazoparib	Adjuvant (gBRCAm, high-risk EBC), Metastatic (gBRCAm)
	PD-1/PD-L1 Inhibitors	Pembrolizumab, Atezolizumab	Adjuvant (high-risk, considering), Metastatic (PD-L1 positive, with chemotherapy)
	Anti-Trop-2 ADCs	Sacituzumab govitecan	Metastatic (after prior treatment)

The role of genetic factors in breast cancer treatment

Genetic factors play an important role in both risk and treatment selection, according to international guidelines.

• BRCA1 and BRCA2 gene mutations:

  • Increases the risk of breast and ovarian cancer

  • Testing for BRCA genes according to NCCN criteria is important in assessing risk and planning prevention. Preventive measures may include surveillance, chemoprevention (e.g., Tamoxifen for BRCA2 mutation carriers), or risk-reducing surgery.

  • For breast cancer patients with BRCA mutations:

    • This has implications for consideration of the use of PARP inhibitors (Olaparib, Talazoparib) in HER2-negative or metastatic TNBC and Olaparib as adjuvant therapy for HER2-negative, high-risk early breast cancer ( OlympiA trial ).

    • Affecting the decision to choose surgical methods and provide genetic counseling to the family.

• Other genes involved: such as PALB2, TP53, PTEN, ATM, CHEK2. Detection of mutations may have implications for surveillance, prevention, and treatment.

New therapies and future directions

Medical science for treating breast cancer is constantly evolving.

• Antibody-Drug Conjugates (ADCs):

  • It is an innovation that delivers chemotherapy drugs precisely to target cancer cells.

  • Fam-trastuzumab deruxtecan (Enhertu) for HER2-positive and HER2-low metastatic breast cancer

  • Sacituzumab govitecan (Trodelvy) for previously treated TNBC and HR+/HER2- metastatic breast cancer.

  • Other ADCs are under development.

• Precision Medicine and Tumor Genomic Profiling:

  • Analysis of genetic changes in tumors ( somatic mutations ) to identify new targets. ESMO recommends genomic profiling if the results would change treatment selection.

  • Liquid Biopsies (ctDNA): Test for cancer DNA in the blood to monitor treatment, detect drug resistance or recurrence.

• Development of immunotherapy:

  • Expanding its use to other subtypes or in combination with other drugs

  • Development of Cancer Vaccines

Post-treatment care and follow-up

Continuity of care and follow-up are important to detect recurrence, manage side effects, and promote quality of life.

• Long-term side effects management: from surgery, radiation therapy, chemotherapy, anti-hormonal drugs

• Follow-up Schedule according to NCCN and ESMO guidelines :

  • NCCN :

    • Physical examination (History and physical exam): Every 6-12 months for 5 years, then annually.

    • Mammogram: First 6-12 months after surgery, then yearly.

  • ESMO (2024) :

    • Post-treatment visits:

      • Years 1-3: Every 3 months (every 6 months for low risk cases)

      • Year 4-5: Every 6 months

      • Subsequent years: Once a year

    • Mammogram: Once a year (both sides after BCS, remaining side after Mastectomy)

    • Breast Ultrasound and MRI: When Necessary

• Physical and Psychosocial Rehabilitation:

  • Exercise, Nutrition, Mental Health, Return to Daily Life

    
    

Table 5: Recommended follow-up schedule after treatment completion (refer to NCCN, ESMO)

Time Since Treatment	Clinical Examination Frequency	Mammogram Frequency	Other tests (as indicated)	Notes
Year 1-3	NCCN: Every 6-12 months ESMO: Every 3 months (or 6 months for low-risk)	Annually (starting 6-12 months after surgery for NCCN)	- Bone density test (for those who received AI) - Gynecological examination (for those who received Tamoxifen) - Breast ultrasound/MRI (ESMO: when necessary)	Inform your doctor immediately if you experience any new unusual symptoms.
Year 4-5	NCCN: Every 6-12 months (to year 5) ESMO: Every 6 months	Once a year	As above	Continue to monitor for any unusual symptoms.
After 5 years	Once a year	Once a year	As above	Still focusing on health care and screening

Note: This table is a general guideline. Follow-up plans for each patient may vary. Follow the instructions of your doctor strictly.

Conclusion

Current breast cancer treatment has evolved significantly, focusing on "personalized medicine" in line with international guidelines such as NCCN, ASCO , and ESMO . Decisions regarding treatment options require a comprehensive assessment of disease stage, molecular characteristics, patient health, and patient needs.

The key is the “Multidisciplinary Team Approach”. Treatment planning and implementation requires the collaboration of specialists from many fields. Joint meetings (e.g. Tumor Board or Breast Cancer Conference) help to ensure that patients receive comprehensive and appropriate care according to international standards.

Despite the challenges, there is hope for continued research and development. The goal is to increase survival, reduce recurrence, and improve the quality of life for patients. Supporting research and providing equitable access to treatment will help patients fully benefit from these advances.

If you have any questions or need more information about breast cancer treatment, please contact Namarak Hospital for consultation with our team of specialist doctors.