Management of Breast Cancer

Slide 1 · Management of Breast Cancer

Pathology-guided local and systemic treatment

Control local disease

Treat systemic risk

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Distinguish local control from treatment of occult or established systemic disease.

Explain why stage, grade, proliferation, and ER/PR/HER2 status change treatment selection.

Connect companion assays with endocrine, HER2-directed, DNA-repair, PI3K, and immune-based therapy.

Interpret neoadjuvant response and integrate pathology into multidisciplinary decisions.

Slide 3 · Two complementary goals of treatment

Local control

Surgery ± radiotherapy

→

Systemic control

Prevent or treat distant metastases

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Long-term outcome

Reduce recurrence; Prolong survival

Effective management addresses both the primary region and clinically occult or evident distant disease.

SCHEMATIC

Slide 4 · Local therapy and systemic therapy treat different risks

LOCAL THERAPY

Targets tumor in breast and regional field

Breast-conserving surgery / mastectomy; Radiotherapy

SYSTEMIC THERAPY

Targets disseminated cancer cells or micrometastases

Endocrine therapy, chemotherapy, and molecularly targeted treatment

Both may be necessary because excision of the primary tumor does not exclude distant spread.

Slide 5 · Extent and biology are independent treatment dimensions

EXTENT / STAGE

Tumor size and regional lymph nodes

Distant metastatic disease

Skin or chest wall involvement

BIOLOGY / PHENOTYPE

Histologic grade and proliferation

ER, PR, and HER2 expression

Actionable molecular alterations

A tumor can be anatomically limited yet biologically aggressive, or extensive but endocrine-responsive.

Slide 6 · Clinical treatment framework

Confirm invasion

Histology and tumor grade

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Establish extent

T, N, M; Local findings

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Characterize biology

ER, PR, HER2; Selected assays

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Integrate modalities

Surgery / RT / systemic

Treatment is chosen by combining pathology with anatomic staging and clinical presentation.

SCHEMATIC

Slide 7 · Three practical clinical biomarker groups

LUMINAL

ER-positive / usually HER2-negative

Endocrine sensitivity is central

HER2-POSITIVE

HER2 overexpression or amplification

Candidate for HER2-directed treatment

TRIPLE-NEGATIVE

ER-, PR-, HER2-negative

Endocrine and conventional HER2 targets absent

Clinical biomarker grouping is useful but does not encompass all molecular heterogeneity.

Slide 8 · The pathology report drives a treatment discussion

Confirm in situ versus invasive carcinoma, histologic subtype, and grade.

Document primary tumor extent, margins, nodal findings, and lymphovascular invasion when assessed.

Provide validated ER/PR/HER2 results and selected molecular findings.

Separate findings that estimate prognosis from those that predict response to a treatment.

Slide 9 · An integrated decision chain

Diagnosis

Morphology and invasion

→

Risk

Stage, grade, nodal status

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Target

ER / HER2 / genomic pathway

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Strategy

Local + systemic plan

There is no single universal treatment for every biologic subtype.

SCHEMATIC

Slide 10 · Anatomic staging describes where disease has spread

The AJCC eighth-edition anatomic framework uses tumor (T), regional nodes (N), and metastases (M).

Stage 0 includes ductal carcinoma in situ; Distant metastasis defines stage IV.

Skin/chest wall infiltration and inflammatory carcinoma alter the assessment of local extent.

Anatomic stage and prognosis are related but not interchangeable.

Slide 11 · Prognostic stage incorporates tumor biology

ANATOMIC COMPONENT

Primary tumor characteristics (T)

Regional nodes (N)

Distant metastases (M)

BIOLOGIC MODIFIERS

Histologic grade

ER and PR expression

HER2; Selected gene assays

The AJCC 8th-edition staging framework; This lecture does not substitute for an updated staging manual.

Slide 12 · Distant spread dominates prognosis

Distant metastasis is the strongest adverse prognostic feature.

Once distant disease is established, cure is uncommon according to the textbook.

Long remissions and meaningful palliation are possible in some endocrine-responsive and HER2-positive tumors.

Systemic treatment intent differs between occult metastatic risk and established metastatic disease.

Slide 13 · Regional nodal status is crucial before distant spread

Axillary lymph-node status strongly predicts outcome in nonmetastatic invasive cancer.

Clinical palpation alone can produce false-positive and false-negative assessments.

Histological examination improves accuracy, including detection of small metastatic deposits.

Nodal assessment helps define risk but does not itself specify a molecular treatment target.

Slide 14 · Sentinel-node mapping limits unnecessary dissection

Primary carcinoma

Drainage through lymphatics

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Sentinel node

First draining node(s)

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Pathologic assessment

Metastasis present or absent

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Regional decision

Extent of further axillary management

Negative sentinel node findings can help avoid morbidity from extensive axillary surgery in appropriately selected patients.

SCHEMATIC

Slide 15 · Primary tumor morphology retains treatment relevance

Tumor size and direct extension inform local extent and resection planning.

Higher histologic grade is associated with poorer prognosis within stage groups.

Lymphovascular invasion signals greater likelihood of recurrence.

Special histologic types may affect expectations of behavior and treatment response.

Slide 16 · Prognostic versus predictive biomarkers

PROGNOSTIC

Estimates natural history or outcomes

Examples: M status, nodal burden, grade, lymphovascular invasion

PREDICTIVE

Estimates response to a specified intervention

Examples: ER for endocrine treatment; HER2 for HER2 blockade

Some measurements (such as ER, HER2, and proliferation) provide both kinds of information.

Slide 17 · ER immunohistochemistry identifies endocrine sensitivity

Nuclear localization

SIMPLIFIED ASSAY SCHEMATIC — NOT MICROSCOPY

Assay: Nuclear estrogen receptor (ER) immunostaining in carcinoma cells.

ER positivity as nuclear expression in ≥1% of tumor cells.

“Low-positive” ER (1%–10%) carries different biology and outcomes from strongly ER-expressing disease.

Slide 18 · PR expression refines luminal interpretation

Nuclear localization

SIMPLIFIED ASSAY SCHEMATIC — NOT MICROSCOPY

PR is assessed by nuclear immunohistochemistry and often accompanies ER positivity.

PR positivity as staining in ≥1% of tumor cells.

Within ER-positive carcinoma, lower PR expression is associated with worse outcomes than strongly coexpressed ER and PR.

Slide 19 · HER2 identifies a targetable receptor axis

Membrane localization

SIMPLIFIED ASSAY SCHEMATIC — NOT MICROSCOPY

HER2 protein expression is assessed by membrane IHC; Gene amplification can be assessed by ISH.

Overexpression commonly reflects HER2 gene amplification.

The result is predictive of response to HER2-directed agents and is also prognostically relevant.

Slide 20 · Proliferation and gene-expression assays refine risk

Ki-67 reflects tumor proliferation, but its use must be interpreted in context.

Gene-expression signatures frequently emphasize proliferation-related transcripts.

Their central clinical role is to identify selected endocrine-responsive cancers unlikely to benefit meaningfully from chemotherapy.

Gene-expression subtype labels are not identical to routine clinical ER/HER2 groups.

Slide 21 · Treatment planning is risk–benefit integration

Selection is driven by both predicted benefit and disease burden.

Histology and biomarkers stratify probable sensitivity.

Tumor and nodal stage quantify the burden requiring local and systemic control.

Therapy can be delivered before or after surgery depending on subtype, stage, and presentation.

Slide 22 · Breast-conserving treatment is common

In many patients, local control is achieved by breast-conserving surgery combined with radiotherapy.

Preservation of breast tissue and elimination of local tumor deposits are compatible goals.

The modality choice depends on local extent and clinical circumstances.

Local treatment does not replace systemic therapy when distant recurrence risk is substantial.

Slide 23 · Breast conservation uses complementary interventions

Breast-conserving surgery

Excise the local carcinoma

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Radiation therapy

Treat residual microscopic local risk

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Clinical follow-up

Assess local and distant outcomes

Surgery plus radiotherapy as a principal local-control strategy.

SCHEMATIC

Slide 24 · Mastectomy is not routinely required for every cancer

Robbins reserves mastectomy mainly for locally advanced disease or selected patients at high risk of a second primary cancer.

A patient at elevated risk may elect mastectomy to reduce the risk of subsequent cancer.

Mastectomy does not automatically eliminate the risk of distant recurrence.

Decisions remain individualized rather than dictated by histologic name alone.

Slide 25 · Locally advanced disease challenges local control

Skin or chest-wall invasion is a marker of locally advanced tumor.

Inflammatory carcinoma is associated with dermal lymphovascular tumor involvement.

Large and invasive tumors may be difficult to control by excision alone.

Stage and presentation influence the sequencing of systemic and local modalities.

Slide 26 · Breast conservation versus mastectomy

BREAST CONSERVATION

Appropriate in many patients

Usually paired with radiation therapy

Preserves breast tissue

MASTECTOMY

Consider for locally advanced disease

Can be a choice in high-risk patients

Does not itself treat occult distant disease

No universal rule for individual operative eligibility is specified in the supplied source.

Slide 27 · Why systemic therapy accompanies local treatment

Some carcinomas disseminate before metastases become clinically evident.

Systemic therapy treats known or presumed distant microscopic disease.

It may also reduce the likelihood of local recurrence.

Treatment selection therefore cannot rest on the success of surgery alone.

Slide 28 · Adjuvant and neoadjuvant describe timing

ADJUVANT

Systemic treatment after primary surgery

Addresses recurrence risk after local excision

Benefit judged by biology and disease burden

NEOADJUVANT

Systemic treatment before definitive surgery

Permits observation of tumor response

Timing depends on stage, subtype, and presentation

These are timing strategies, not separate drug classes.

Slide 29 · Neoadjuvant treatment creates an in vivo response test

Pretreatment biopsy

Grade and biomarker profile

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Systemic therapy

Biology-specific regimen

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Resection pathology

Measure residual tumor

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Clinical interpretation

Response informs prognosis

Response is a particularly informative prognostic indicator for HER2-positive and triple-negative carcinoma.

SCHEMATIC

Slide 30 · Pathologic complete response has subtype dependence

Pathologic complete response (pCR) denotes absence of residual invasive carcinoma under the relevant pathology definition.

Strong pCR responses to chemotherapy with HER2-positive and triple-negative cancers.

Response to neoadjuvant therapy is a strong prognostic factor in these groups.

The same prognostic inference is less reliable for most luminal cancers.

Slide 31 · Chemotherapy benefit varies by proliferation

Cytotoxic chemotherapy is emphasized for highly proliferative cancers.

High proliferation may occur in more than one clinical molecular subtype.

Tumor burden and patient presentation contribute to the decision and timing.

Avoid treating “breast cancer” as a single chemotherapy-sensitive disease.

Slide 32 · Luminal A and high-proliferation disease differ

MINIMALLY PROLIFERATIVE LUMINAL A

Strong endocrine sensitivity

Low expected chemotherapy benefit

Consider how a genomic assay may refine risk

HIGHLY PROLIFERATIVE CARCINOMA

Greater rationale for cytotoxic chemotherapy

May occur across clinical molecular groups

Subtype-specific targeted therapy can coexist

Avoid inferring drug efficacy from ER status alone.

Slide 33 · Endocrine therapy is central to many luminal cancers

The treatment exploits estrogen-dependent growth rather than indiscriminate cytotoxic injury.

ER nuclear staining provides an essential companion diagnostic.

Agents can reduce estrogen supply, block receptor signaling, or degrade ER.

Treatment is particularly important in endocrine-responsive, low-proliferation disease.

Slide 34 · Three endocrine strategies

Reduce estrogen

Ovarian suppression / aromatase inhibitors

→

Block receptor

Tamoxifen

→

Degrade receptor

Fulvestrant

These distinct mechanisms converge on lowering estrogen receptor–mediated growth signaling.

SCHEMATIC

Slide 35 · Estrogen deprivation removes an upstream stimulus

Oophorectomy or ovarian suppression reduces ovarian estrogen stimulation in appropriate patients.

Aromatase inhibitors such as letrozole reduce estrogen biosynthesis.

Both are listed among endocrine approaches Table 23.7.

Hormonal milieu and clinical setting determine which approach is suitable.

Slide 36 · Tamoxifen acts at the estrogen receptor

Tamoxifen is listed as an ER-blocking treatment.

Target presence is established by ER immunohistochemistry.

This strategy directly limits estrogen receptor signaling rather than acting as standard cytotoxic chemotherapy.

ER-negative tumors generally lack the corresponding target.

Slide 37 · Fulvestrant promotes ER degradation

Fulvestrant is presented as a receptor-degrading endocrine treatment.

Reducing functional ER addresses a different intervention point from lowering estrogen availability.

Receptor biology and acquired resistance affect therapeutic selection.

Management of metastatic resistance also requires molecular reassessment when indicated.

Slide 38 · Endocrine treatment: Cytostatic versus cytotoxic

CYTOSTATIC EFFECT

Restrains proliferation driven by ER signaling

May achieve disease control without direct bulk cytotoxicity

CYTOTOXIC EFFECT

Damages or kills malignant cells

More relevant to chemotherapy and some antibody–drug conjugates

Robbins explicitly characterizes endocrine treatment as effective cytostatic—not cytotoxic—therapy for ER-positive cancer.

Slide 39 · CDK4/6 inhibition restrains cell-cycle progression

ER-positive cancer

Mitogenic proliferation signals

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CDK4/6

Cell-cycle regulatory kinases

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Kinase inhibitors

Palbociclib / ribociclib / abemaciclib

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Growth restraint

Often combined with endocrine treatment

CDK4/6 inhibition in ER-positive cancer, usually with an aromatase inhibitor.

SCHEMATIC

Slide 40 · Interpreting Ki-67 in a CDK4/6 discussion

Ki-67 IHC estimates proliferative activity, an important tumor-biologic feature.

Robbins Table 23.7 lists Ki-67 under companion assays for CDK4/6 inhibitors.

Ki-67 should not be presented as a universally sufficient standalone eligibility test.

Interpret proliferation alongside receptor status, stage, and clinical context.

Slide 41 · Endocrine resistance can have a molecular mechanism

ESR1 mutations may produce ligand-independent ER activation.

ESR1 alterations in endocrine-resistant metastatic ER-positive breast cancer.

Testing at relapse or progression on endocrine treatment can guide therapeutic decisions.

A tumor may retain an ER-driven phenotype while losing sensitivity to earlier endocrine strategies.

Slide 42 · A luminal cancer can evolve under endocrine therapy

Initial ER-positive tumor

Treatment-sensitive signaling

→

Endocrine exposure

Selective therapeutic pressure

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ESR1-mutant clone

Constitutive receptor activation

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Molecular reassessment

Reconsider drug mechanism

Conceptual illustration of one documented resistance pathway; It does not represent every resistant carcinoma.

SCHEMATIC

Slide 43 · Genomic assays can reduce unnecessary chemotherapy

Selected mRNA-expression profiles identify lower-risk, endocrine-responsive cancers.

Their principal value is to help recognize patients who are unlikely to gain appreciably from chemotherapy.

Results supplement—not replace—histology, stage, and ER/HER2 testing.

Assay utility is context-dependent; The textbook does not mandate use in every patient.

Slide 44 · HER2-targeted therapy is a biomarker–drug match

HER2 protein overexpression or genomic amplification identifies a therapeutically actionable driver.

Pathology establishes receptor status by IHC and appropriate molecular assays.

Antibodies, antibody–drug conjugates, and kinase inhibitors act at different therapeutic levels.

Targeted therapy can be integrated with systemic cytotoxic treatment.

Slide 45 · HER2-targeted approaches

HER2 receptor

Target on tumor cell

→

Blocking antibody

Trastuzumab

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HER2-linked payload

T-DM1

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Kinase inhibition

E.g., lapatinib

Table 23.7 lists antibodies, antibody–drug conjugates, and tyrosine kinase inhibitors as therapeutic classes.

SCHEMATIC

Slide 46 · Trastuzumab targets HER2-positive carcinoma

Trastuzumab is a monoclonal antibody directed at HER2.

Its rationale depends on target expression/amplification in tumor cells.

HER2-targeted treatment is not interchangeable with endocrine therapy.

HER2 status must be reliably measured and interpreted before selecting this class.

Slide 47 · T-DM1 links a HER2 antibody to cytotoxic therapy

T-DM1 (trastuzumab emtansine) is an antibody–drug conjugate.

The antibody delivers a cytotoxic payload to cells selected by HER2-directed binding.

It combines target recognition with a cytotoxic treatment mechanism.

HER2 assessment remains central to this approach.

Slide 48 · Tyrosine kinase inhibition targets HER2 signaling

Lapatinib as a HER2-associated tyrosine kinase inhibitor.

The target is receptor-associated growth signaling rather than circulating estrogen.

Molecular selection remains essential because the pathway is not uniform across tumors.

Specific drug choices and regimens require clinical guideline verification beyond the textbook.

Slide 49 · HER2 testing connects morphology with treatment

Membrane localization

SIMPLIFIED ASSAY SCHEMATIC — NOT MICROSCOPY

HER2 IHC assesses membrane protein expression.

In situ hybridization (ISH) evaluates HER2 amplification when indicated.

Robbins also lists DNA sequencing for HER2 mutations in relevant contexts.

Slide 50 · Homologous recombination deficiency creates vulnerability

BRCA1 / BRCA2 dysfunction

Impaired homologous recombination

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DNA damage

Greater repair stress

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PARP inhibition

Alternative repair blocked

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Therapeutic vulnerability

Select DNA-repair-deficient tumors

Schematic summary of the homologous-recombination repair / PARP rationale in Table 23.7.

SCHEMATIC

Slide 51 · BRCA alterations act as predictive biomarkers

Germline BRCA1 or BRCA2 pathogenic variants identify a recognized PARP-inhibitor-responsive group.

DNA sequencing as the companion approach.

Other mechanisms of homologous recombination deficiency may be relevant but are less conclusively established in the text.

Do not equate every triple-negative tumor with BRCA-deficient disease.

Slide 52 · PARP inhibition exploits altered repair capacity

Olaparib is the PARP inhibitor example given by Robbins.

The therapeutic idea depends on susceptibility created by homologous recombination repair defects.

This is a genetically informed treatment strategy rather than a therapy for all breast cancers.

Clinical eligibility must be determined by the relevant treatment setting and validated genomic findings.

Slide 53 · PI3K–AKT–mTOR is another therapeutic pathway

PIK3CA / pathway activation

Growth and survival signaling

→

PI3K inhibition

Alpelisib

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MTOR inhibition

Everolimus

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Treatment context

Advanced ER+ / HER2− carcinoma

Selected advanced luminal cancers and the predictive value of PIK3CA mutation for PI3K-directed therapy.

SCHEMATIC

Slide 54 · PIK3CA testing is a drug-selection tool

Activating PIK3CA mutation is a companion marker for PI3K inhibition.

Sequencing can identify the actionable alteration.

PI3K-pathway changes are common but not every alteration necessarily predicts the same drug response.

The context highlighted is advanced ER-positive, HER2-negative carcinoma.

Slide 55 · MTOR and PI3K inhibitors act at distinct nodes

Everolimus inhibits mTOR signaling.

Alpelisib is a PI3K-targeted inhibitor.

Both are pathway-oriented, but target and biomarker logic must not be conflated.

Clinical selection depends on molecular results and the therapy setting.

Slide 56 · Immunotherapy depends on tumor–immune context

Checkpoint blockade is relevant in selected high-grade, ER-negative cancers.

Checkpoint proteins include PD-1/PD-L1 and CTLA-4.

Immune biomarkers as predictors only in defined settings.

Immune therapy is not a default treatment for every ER-negative tumor.

Slide 57 · Checkpoint inhibition releases an immune brake

Tumor–immune interface

Inhibitory checkpoint signaling

→

Checkpoint antibody

PD-1 / PD-L1 blockade

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T-cell response

Reduced inhibitory signaling

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Selected patients

Benefit depends on clinical context

Illustrative mechanism; The specific example drugs and permitted indications are context dependent.

SCHEMATIC

Slide 58 · Immune biomarkers have different meanings

PD-L1 immunohistochemistry is one companion assay.

Tumor mutational burden (TMB) may inform immunotherapy eligibility in particular settings.

Mismatch repair deficiency (MMRD) or microsatellite instability (MSI) is rare in breast cancer but may be actionable.

Do not treat PD-L1, TMB, and MMRD as interchangeable measurements.

Slide 59 · Tumor-infiltrating lymphocytes carry response information

TILs are mononuclear inflammatory cells in tumor and associated stroma.

Prominent TILs with better prognosis and response to neoadjuvant chemotherapy in TNBC and HER2-positive cancers.

This is biologic context, not a substitute for validated receptor testing.

Pathologists should distinguish an immune infiltrate from an immune-drug companion assay.

Slide 60 · TROP2 can carry a cytotoxic payload

TROP2 is a cell-surface glycoprotein expressed by many triple-negative carcinomas.

Sacituzumab govitecan is the TROP2-directed antibody–drug conjugate example.

The payload is cytotoxic while antibody binding provides target-oriented delivery.

Optimal response-predictive assays remain under investigation.

Slide 61 · Antibody blockade versus antibody–drug conjugate

BLOCKING ANTIBODY

Binds target receptor / signaling protein

Example: Trastuzumab against HER2

ANTIBODY–DRUG CONJUGATE

Antibody guides attached cytotoxic payload

Examples: T-DM1 (HER2); Sacituzumab govitecan (TROP2)

Similar antibody architecture does not imply the same mode of action.

Slide 62 · Biomarker-to-treatment matrix

Tumor finding

Therapeutic class

Companion evidence

ER nuclear expression

Endocrine therapy

ER IHC

HER2 overexpression / amplification

HER2-directed agents

HER2 IHC / ISH

Germline BRCA1/2 alteration

PARP inhibitor

Validated germline DNA testing

PIK3CA activating alteration

PI3K inhibitor

Validated mutation assay

Selected immune phenotype

Checkpoint inhibitor

Context-specific PD-L1 / TMB / MMRD

Slide 63 · Case 1 · ER-positive, low-proliferation cancer

HYPOTHETICAL TEACHING CASE

A resected invasive carcinoma has strong nuclear ER expression, is HER2-negative, and has low proliferation.

REASONING

Classify this as an endocrine-responsive phenotype; Stage and nodal findings still determine recurrence risk.

INTERPRETATION

Endocrine therapy and a potentially limited contribution from chemotherapy in minimally proliferative luminal cancers.

Slide 64 · Case 2 · Highly proliferative luminal carcinoma

HYPOTHETICAL TEACHING CASE

An invasive carcinoma expresses ER but shows higher proliferation and adverse histologic features.

REASONING

ER positivity alone does not eliminate the rationale for cytotoxic chemotherapy.

INTERPRETATION

Assess extent, grade, nodal status, and potential genomic risk information alongside endocrine sensitivity.

Slide 65 · Case 3 · HER2-positive carcinoma after neoadjuvant treatment

HYPOTHETICAL TEACHING CASE

A core biopsy shows invasive, HER2-positive carcinoma. Systemic therapy precedes surgery.

REASONING

A carefully documented pathology assessment of residual disease is needed after treatment.

INTERPRETATION

Neoadjuvant response conveys prognostic information in HER2-positive disease; HER2-directed therapy rests on verified target status.

Slide 66 · Case 4 · Triple-negative tumor with inherited DNA-repair defect

HYPOTHETICAL TEACHING CASE

An invasive tumor lacks ER, PR, and HER2; Germline testing identifies a BRCA1 alteration.

REASONING

The clinical phenotype and the germline predictive biomarker answer different questions.

INTERPRETATION

High proliferation supports chemotherapy consideration; BRCA-associated repair deficiency provides rationale for PARP-targeted treatment in appropriate contexts.

Slide 67 · Case 5 · Endocrine-treated disease progresses

HYPOTHETICAL TEACHING CASE

A previously endocrine-responsive metastatic ER-positive cancer progresses during hormone-directed treatment.

REASONING

Progression may reflect acquired resistance; ESR1 mutation testing is one documented strategy.

INTERPRETATION

Molecular reassessment can change treatment selection even when the original biopsy established ER positivity.

Slide 68 · Case 6 · Locally advanced breast cancer

HYPOTHETICAL TEACHING CASE

A primary carcinoma clinically involves skin and regional nodes, with no distant metastasis documented in the scenario.

REASONING

Local therapy is challenging, and the order of treatment depends on subtype, stage, and presentation.

INTERPRETATION

Integrate systemic treatment planning with local modalities rather than relying on an excision-only strategy.

Slide 69 · Pathology-to-therapy sign-out checklist

Morphology

In situ vs invasive; Type; Grade

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Extent

Size; Margins; Nodes; LVI

→

Validated biomarkers

ER / PR / HER2

→

Selective assays

BRCA / PIK3CA / ESR1 / immune

→

Integrated discussion

Risk, response, treatment

Report only examinations actually performed; Results require appropriate methods and interpretation.

SCHEMATIC

Slide 70 · Limitations of source-based treatment teaching

SUPPORTED BY ROBBINS

Conceptual goals and modalities

Biology-driven treatment classes

Examples of drug targets and assays

NOT ESTABLISHED HERE

Current drug approvals in every region

Patient-specific regimen, dosing or sequencing

Complete 2026 guideline eligibility rules

Therapy tables are educational; Institutional protocols and current oncology guidelines determine actual prescribing.

Slide 71 · Three durable principles

Control the breast and regional disease; Treat systemic risk; Target the biology.

Disease extent determines anatomic risk and feasibility of local treatment.

ER, HER2, DNA-repair, PI3K, and selected immune markers can predict treatment sensitivity.

Response to neoadjuvant treatment adds prognostic information, especially in HER2-positive and triple-negative carcinomas.

Slide 72 · Core reference and interpretation boundaries

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Chapter 23, The Breast: Invasive Carcinoma of the Breast (pp. 954–967).

Management of Breast Cancer (pp. 965–966); Table 23.7, Targeted Treatment of Breast Cancer (p. 966).

Prognostic and Predictive Factors; Breast Cancer Staging; Tables 23.5–23.6 (pp. 964–965).

Treatment examples reflect the supplied textbook rather than a separately verified, contemporary prescribing guideline.