Breast Cancer Staging

Breast cancer staging assesses the size and spread of cancer to help doctors plan treatment and estimate the prognosis as accurately as possible. The new AJCC system, 8th edition, implemented in 2018, represents the most significant change in 60 years. It incorporates biomarkers such as hormone receptors (ER, PR), HER2, and multigene panel results into the assessment of tumor size (T), lymph nodes (N), and metastasis (M). This means that patients with the same "anatomical" staging may have significantly different "prognostic" staging.

This article from Numarak Hospital, a specialized breast cancer center in Bangkok, explains in detail the AJCC 8th edition staging system for breast cancer, to help patients and their families better understand their medical reports.

Why is staging breast cancer important?

Breast cancer staging is a common language used for communication among doctors worldwide, beginning in 1959 by the American Joint Committee on Cancer (AJCC) to enable doctors to:

• Plan the most appropriate treatment for each individual patient.

• Assess the prognosis, survival rate, and chances of recurrence.

• Compare treatment outcomes between healthcare facilities and research studies.

• Monitoring the response of patients receiving preoperative (neoadjuvant) treatment.

Since the first edition of the AJCC guidelines was published in 1977, the system has been periodically updated. The 8th edition, officially implemented on January 1, 2018, is the most significant update as it concretely incorporates personalized medicine technology.

Previously, some patients with "same stage" cancer still had vastly different survival rates and treatment responses because the old system did not take into account the biological characteristics of the tumor , which determine both the severity and the response to specific drug regimens. The improvements in the 8th edition therefore lead to significantly more accurate assessments.

The main changes in the 8th AJCC.

The 8th edition of AJCC contains four important changes that patients and families should be aware of:

1. Use two spacing systems simultaneously.

• Anatomic Stage: Use T, N, M as before for hospitals in countries where biomarker testing is not available.

• Prognostic Stage: Combines T, N, M with tumor grade, ER, PR, HER2, and multigene panel — this system is primarily used in countries with advanced technology, including Thailand.

2. Utilize biomarkers.

All patients with advanced breast cancer must have their ER, PR, HER2 levels, and severity grade checked to calculate the prognostic stage.

3. Limb carcinoma (LCIS) is no longer stage 0 cancer.

Issue No. 7: LCIS (Lobular Carcinoma in Situ) is in the Tis group (stage 0).

Issue 8: LCIS is considered a benign (non-cancerous) lesion, but it is a risk factor for future cancer.

4. Post-neoadjuvant treatment schedule before surgery.

Patients who received neoadjuvant chemotherapy before surgery will be re-evaluated with the prefix "yp" to indicate a post-treatment evaluation.

Anatomic Staging

This system evaluates three components: T (Tumor), N (Node), and M (Metastasis). Each component is prefixed with a word:

• c = Clinical (Assessed based on physical examination and photographs)

• p = Pathologic (assessed from post-surgical pathology results)

• yp = Post-neoadjuvant (evaluation after chemotherapy and surgery)

Important: Medical images used for staging must be taken within 4 months before or after diagnosis/surgery, provided the disease is not worsening.

T: Size and characteristics of the tumor.

The T-system is categorized based on the size of the largest "invasive" (invasive) portion:

Distance T	Size/Characteristics
Tis	Stage 0 cancer — Ductal Carcinoma in Situ (DCIS) or Paget disease, which is non-invasive.
T1mi	Invasive nodules ≤ 1 mm (microinvasive)
T1a	> 1 mm but ≤ 5 mm
T1b	> 5 mm but ≤ 10 mm
T1c	> 10 mm but ≤ 20 mm
T2	> 20 mm but ≤ 50 mm
T3	> 50 mm
T4a	It spreads to the chest wall.
T4b	Spread of skin ulcers (satellite nodules, peau d'orange)
T4c	T4a + T4b together
T4d	Inflammatory breast cancer

Key points that patients should understand:

• If there are multiple nodes (multifocal/multicentric), the size of the "largest" node is used as the criterion; they are not combined, but the letter "m" is added to the end, e.g., T2(m).

• Small pieces less than 2 mm but greater than 1 mm should be rounded to 2 mm. (New in issue 8)

• Invasion confined to the pectoralis muscle (below the breast) does not count as T4a — it must extend to the ribs or intercostal/serratus muscles to be counted.

• Inflammatory breast cancer (T4d) is a "clinical" diagnosis requiring the presence of redness, swelling, and an orange peel-like texture in at least one-third of the breast, and its rapid onset within several weeks to months.

N: Lymph node metastasis.

The axillary lymph nodes are divided into three levels based on the location of the pectoralis minor muscle:

• Level I: Located on the outer edge of the pectoralis minor muscle.

• Level II: Located beneath the pectoralis minor muscle (including Rotter's nodes).

• Level III: Located on the inner edge of the pectoralis minor (infraclavicular) muscle.

Distance N	meaning
cN0	No lymph node metastasis was found during physical examination and imaging.
cN1	The lymph nodes on the same side have spread to level I-II and are motile.
cN2a	Infected or lodged in level I-II lymph nodes on the same side.
cN2b	The infection spreads only to the internal mammary (IM) lymph nodes, excluding the armpit.
cN3a	Invasive to level III (infraclavicular) lymph nodes.
cN3b	Invasive IM with level I-II
cN3c	The lymph nodes on the same side have spread to the supraclavicular lymph nodes.

Key points to note:

• Cervical lymph nodes, opposite axillary lymph nodes, IM and opposite supraclavicular lymph nodes → are considered distant metastasis (M1).

• If the tissue sample is from a sentinel lymph node biopsy (SLNB), enter "(sn)", e.g., pN1(sn).

• If using a needle biopsy (FNA or core biopsy) → enter "(f)", e.g., cN1(f).

• If no lymph nodes are evaluated, use cN0 as the default value (unless all lymph nodes have been removed, then use cNX).

M: Spread to other organs.

Distance M	meaning
cM0	No spread was found from physical examinations and photographs.
cM0(+)	Tumor cells (< 2 mm) were detected in the blood, bone marrow, or other lymph nodes, without symptoms.
cM1	Spread can be detected through photographs or physical examinations.
pM1	Confirmed by pathology (tumor deposit > 0.2 mm).

Important: pM0 is not present in this system — because the absence of pM0 in other organ biopsies does not confirm the absence of metastasis elsewhere.

The organs where breast cancer most commonly metastasizes include the bone, lungs, brain, and liver.

According to NCCN guidelines, patients with early-stage breast cancer (T0–3 N1 M0 or T1–3 N0–1 M0) who are asymptomatic do not necessarily need a CT scan, bone scan, or whole-body PET/CT scan. These scans are performed only if:

• Stage IIIA or higher cancer.

• Inflammatory breast cancer

• We are considering chemotherapy before surgery.

• There are abnormal symptoms indicating metastasis (bone pain, chronic cough, weight loss, etc.).

Prognostic Staging

This is at the heart of the change in AJCC 8th edition — integrating biological properties with T, N, and M.

Tumor Grade

The Scarff-Bloom-Richardson system, standardized by the Nottingham group, is used to evaluate three characteristics:

• Gland formation (tubule formation)

• Nuclear pleomorphism

• Cell division (mitotic count)

Each item is scored 1–3, for a total score:

• Grade 1 (3-5 points): Well-differentiated — The tumor is well differentiated, and the prognosis is good.

• Grade 2 (6-7 points): Moderately differentiated — Intermediate level

• Grade 3 (8-9 points): Poorly differentiated — The mass is not distinguishable; worse prognosis.

Data from the SEER Program (161,708 cases) confirms that grade is an important predictive factor, independent of nodule size or the number of lymph nodes.

Hormone receptors (ER, PR) and HER2.

In issue number 8, all patients with advanced breast cancer must undergo ER, PR, and HER2 testing.

ER (Estrogen Receptor) and PR (Progesterone Receptor):

• If "positive" → hormone-responsive tumor → treatment with Selective Estrogen Receptor Modulators (SERMs) such as tamoxifen or aromatase inhibitors.

• The higher the receptor expression level → the more effective hormone therapy is.

• Sequence of response: ER+/PR+ > ER+/PR- > ER-/PR+ > ER-/PR-

HER2 (Human Epidermal Growth Factor Receptor 2):

• The presence of HER2 amplification or overexpression → worse prognosis (historically).

• It is more common in invasive ductal carcinoma than invasive lobular carcinoma.

• It is often associated with a high tumor grade, a high rate of cell division, and a negative ER/PR result.

• However! The availability of anti-HER2 drugs such as trastuzumab significantly improves the prognosis for this patient group — in issue 8, HER2-positive patients often experience a downstaging of the prognosis.

Multigene Panel Testing

Issue 8 approves Oncotype DX Breast Recurrence Score — a test of 21 genes' expression to predict the likelihood of recurrence.

Use in these cases:

• Blocks sized T1-T2 (≤ 5 cm)

• Lymph nodes are negative (N0).

• ER positive

• HER2 negative

Interpretation of results:

• Score < 11 → Low risk → No additional benefit from chemotherapy → Classified as Stage IA (downstage).

• Score 11-25 → Moderate risk — Decision should be made in conjunction with other factors.

• Score > 25 → High risk → Chemotherapy should be considered.

Limitations: Multigene panel testing is still expensive, and therefore not widely accessible in many countries.

Biological Subtypes

Through genetic studies, researchers have discovered that breast cancer can be divided into four subgroups with distinct behaviors:

Subtype	nature	Disease forecast	Treatment that responds.
Luminal A-like	High ER+/PR+, low HER2-, low Ki-67, often grade 1-2.	Very good (5-year survival > 80%)	Endocrine therapy is very effective; chemotherapy is less effective.
Luminal B-like	Low ER+/PR+, HER2- (or + in some cases ~30%), high Ki-67, often grade 3.	Average — Worse than Luminal A	Chemotherapy is more effective than endocrine therapy.
HER2-enriched	HER2+, ER/PR may be positive or negative, usually grade 3.	Much better after taking anti-HER2 medication.	Trastuzumab + Chemotherapy
Basal-like (Triple-Negative)	ER-, PR-, HER2-, usually grade 3.	Worst	There is some response to chemotherapy, but there is no specific targeted therapy.

Triple-Negative Breast Cancer (TNBC): Breast cancer that lacks ER, PR, and HER2 receptors — the most challenging to treat. Often found in younger patients and with a high grade.

Examples of phase changes: Upstaging and Downstaging.

An analysis of 501,451 patients in the National Cancer Database, when transitioning from the 7th to the 8th edition, revealed the following:

• Approximately 23% of patients in stages I-III are downstaged.

• Approximately 19% of patients in stages I-III are upstaged.

Examples of distance changes:

T	N	M	Grade	ER	PR	HER2	Onco<11	AJCC 7	AJCC 8	Change
1	0	0	1	-	-	-	N/A	IA	IB	⬆ Upstage (TNBC)
2	0	0	3	+	-	-	N/A	IIA	IIB	⬆ Upstage
2	0	0	Any	+	+	-	Yes	IIA	IA	⬇ Downstage
3	1	0	1	+	+	+	N/A	IIIA	IIA	⬇ Downstage
3	0	0	1	+	+	+	N/A	IIB	IB	⬇ Downstage

Real-life case study:

Case 1 — Upstage (from IIA to IIIB):

A 34-year-old woman presents with a 2.5 cm mass with one node metastasis → T2N1M0 = Stage IIA (AJCC 7), but the mass is triple-negative grade 2 → Stage IIIB (AJCC 8) — Upstage.

Case 2 — Downstage (from IIB to IB):

A 47-year-old woman with a 5.6 cm mass, no nodes → T3N0M0 = Stage IIB (AJCC 7), but the mass is Grade 1, ER+/PR+/HER2+ → Stage IB (AJCC 8) — Downstage.

Case 3 — Upstage (from IA to IIA):

A 49-year-old woman with a 1.7 cm mass, no nodes → T1N0M0 = Stage IA (AJCC 7), but the mass is triple-negative grade 3, Ki-67 90% → Stage IIA (AJCC 8) — Upstage.

This information significantly changed treatment decisions — patients in "Case 3" should receive chemotherapy before surgery, even if the tumor is small.

The role of photographic inspection in distance setting.

Medical imaging is fundamental to staging breast cancer, particularly the clinical stage before surgery.

Mammogram (including Digital Breast Tomosynthesis - DBT)

• Suitable for detecting microcalcifications.

• DCIS is well visible (approximately 75% of DCIS is shown as calcification only).

• Accuracy decreases in dense breasts.

• DBT helps increase the cancer detection rate in screening, but its effectiveness is limited in certain stages.

Ultrasound

• Used to assess size and location, especially in firm breasts.

• Axillary and supraclavicular lymph nodes were examined well.

• Assistance with image-guided biopsy.

• Weakness: Accuracy is operator-dependent.

MRI (Magnetic Resonance Imaging)

Strengths:

• Best viewed for invasive lobular carcinoma (where mammograms and ultrasounds often underestimate its true size).

• Multifocal/multicentric disease is best seen here.

• The chest wall and pectoralis muscle are clearly visible.

• It is best used to monitor the response to neoadjuvant chemotherapy (PPV 93%).

weakness:

• The size is often overestimated compared to the pathology results.

• Low specificity — non-cancerous enhancements may be observed (biopsy required for confirmation).

• High cost

When imaging data is conflicting: According to AJCC Rule 8, the MRI results should prevail.

FDG PET/CT

• Used in patients with stage IIIA or higher.

• Detect distant metastasis and regional nodal disease that are not visible in other imaging techniques.

• The internal mammary and supraclavicular nodes were well assessed.

At Numarak Hospital , 3D mammograms (Digital Breast Tomosynthesis with AI) are used in conjunction with ultrasound and MRI to accurately assess the size and extent of cancer.

The effect of spacing on treatment.

More precise spacing impacts treatment decisions in several areas:

1. Decide between breast-conserving surgery vs. total mastectomy.

• Size of the tumor, multifocal/multicentric location, and skin/nipple invasion → Decide which type of surgery to perform.

• Presence of calcium deposits less than 2 cm from below the nipple and Paget disease → Nipple-sparing mastectomy is contraindicated.

2. Management of axillary lymph nodes.

• The ACOSOG Z0011 study found that patients with 1-2 positive sentinel nodes who met the criteria did not require total lymph node dissection (ALND).

• Patients receiving neoadjuvant chemotherapy often undergo targeted axillary dissection, where a clip is implanted in the node for later retrieval.

3. Make a decision about chemotherapy.

• The effect of oncotype DX in ER+/HER2-/N0 → determines whether chemotherapy is necessary.

• Most triple-negative and HER2-positive patients receive neoadjuvant chemotherapy before surgery.

4. Radiotherapy planning.

• Level III invasion, internal mammary or supraclavicular nodes → Adjust radiation field.

5. Individualized disease prognosis.

• Patients and their families understand their true prognosis in order to make treatment decisions and plan their lives.

Limitations of resizing.

Although AJCC Edition 8 represents a significant development, it also has limitations:

• Biomarker and multigene panel testing is expensive, making it inaccessible to some healthcare facilities.

• In low- and middle-income countries, the traditional TNM system remains the primary standard.

• In Europe and some other countries, policy, disbursement, and regulatory obstacles prevent its widespread use compared to the United States.

• The complexity — the numerous combinations of T, N, M, grade, ER, PR, and HER2 — requires physicians to refer to tables.

In Thailand, specialized breast cancer hospitals, including Numarak Hospital, use the AJCC 8th edition system as a standard because it has the technology for biomarker and multigene panel testing.

Frequently Asked Questions (FAQ)

What is the difference between breast cancer stage AJCC 7 and AJCC 8?

The 7th edition of the AJCC used only tumor size (T), lymph nodes (N), and metastasis (M) for staging. The 8th edition added biomarkers including severity grade, hormone receptors (ER, PR), HER2, and multigene panel results to the staging calculation, resulting in different prognostic stages for patients with the same tumor size.

Why did my doctor say my period had changed after receiving my ER, PR, and HER2 test results?

This is the result of using AJCC Edition 8. The initial stage (anatomic stage) uses only the size of the tumor and lymph nodes. Once biomarkers are obtained, the doctor will calculate the "prognostic stage," which more accurately reflects your actual disease prognosis. This may result in a downstage or an upstage.

What is a triple-negative diagnosis, and why does it have a worse prognosis?

Triple-Negative Breast Cancer (TNBC) is a type of breast cancer that does not express ER, PR, or HER2 receptors, and therefore does not respond to hormone therapy or anti-HER2 drugs. The prognosis is therefore worse than other cancers at the same stage. However, new treatments such as immunotherapy and PARP inhibitors have improved treatment outcomes.

How important is the Oncotype DX result?

This is very important for ER+/HER2-/N0 patients with T1-T2 tumors — because an Oncotype DX score < 11 indicates that chemotherapy is not necessary; treatment with hormone therapy alone is possible, which reduces side effects and costs. In the 8th edition of the AJCC, a low score can also reduce the stage to IA.

Is LCIS in my pathology results considered cancerous?

In the eighth edition, LCIS (Lobular Carcinoma in Situ) is no longer considered cancerous, but rather a lesion that increases the risk of developing breast cancer in the future (therefore requiring regular monitoring). However, pleomorphic LCIS, or necrosis, may require surgical removal, similar to DCIS.

Why does the MRI image show the tumor as larger than a mammogram?

MRI is highly sensitive and often slightly overestimates size compared to pathological results. Mammograms in tight breasts may underestimate the true size, especially in invasive lobular carcinoma — when imaging values conflict, the AJCC recommends using MRI values as the criterion.

Why is inflammatory breast cancer immediately classified as T4d?

Inflammatory breast cancer is diagnosed based on clinical symptoms (not tumor size), namely redness, swelling, and an orange peel-like texture on at least one-third of the breast, occurring rapidly within weeks to months. It is a rapidly spreading cancer that penetrates the lymphatic system in the skin, and is therefore always classified as T4d and stage IIIB or higher. Neoadjuvant chemotherapy is the first-line treatment.

What stage are multiple lumps in the breast (multifocal/multicentric) considered to be?

AJCC uses the size of the "largest" nodule to determine the T category, not including smaller nodule sizes, but uses the letter "(m)", e.g., T2(m), to indicate multiple nodules. However, the presence of multiple nodules may change the surgical plan from lumpectomy to mastectomy, so reporting the location and size of each nodule is very important.

I received chemotherapy before surgery. What stage of my treatment was?

Patients receiving neoadjuvant chemotherapy use the prefix "yp" after surgery, such as ypT1ypN0. Post-treatment outcomes are often better than pre-treatment outcomes if there is a response to the medication (downstaging). In HER2+ and triple-negative patients, a pathologic complete response (pCR) , meaning no residual cancer is found, is a positive sign for long-term prognosis.

About Numarak Hospital

Numarak Hospital is one of the first specialized breast cancer centers in Thailand, founded by Associate Professor Dr. Yaowanuch Kongdan. Located on Phetchaburi Road, Bangkok, it provides comprehensive breast cancer screening, diagnosis, and treatment (one-stop breast care) under the concept of "like visiting a friend's house."

The hospital utilizes internationally recognized technologies for diagnosis, including:

• 3D Mammogram with AI (Digital Breast Tomosynthesis)

• Specialized Breast MRI

• Ultrasound and biopsy in one procedure.

• ER, PR, HER2, and Oncotype DX testing.

• IORT (Intraoperative Radiation Therapy) is a treatment involving radiation therapy performed in the operating room.

• Scout Radar Localization for undetectable masses.

The medical team at Namarak Hospital uses the AJCC 8th edition staging system as a standard for evaluating all patients in order to provide personalized medicine that best matches the biology of the tumor and the condition of each individual patient.

Content reviewed by: The medical team at Namarak Hospital.

Main reference:

• Hortobagyi GN, Connolly JL, D'Orsi CJ, et al. Breast. In: AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.

• Giuliano AE, Connolly JL, Edge SB, et al. Breast cancer—major changes in the AJCC eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:290-303.

• Zhu H, Doğan BE. AJCC Staging System for Breast Cancer, 8th Edition: Summary for Clinicians. Eur J Breast Health. 2021;17(3):234-238.

• Teichgraeber DC, Guirguis MS, Whitman GJ. Breast Cancer Staging: Updates in the AJCC 8th Edition and Current Challenges for Radiologists. AJR. 2021;217:278-290.

• Weiss A, Chavez-MacGregor M, Lichtensztajn DY, et al. Validation study of the AJCC eighth edition prognostic stage. JAMA Oncol. 2018;4:203-209.

Note: The information in this article is for general knowledge purposes only and is not personalized medical advice. Please consult a specialist physician for diagnosis and treatment appropriate to your condition.