Breast cancer

Breast cancer develops when cells in breast tissue become malignant, usually involving the lining of ducts or lobules. It includes diseases with different biology. Two people with the same-sized lump may need different treatment because their receptor results, lymph nodes and overall health differ.

In situ, invasive and metastatic

Ductal carcinoma in situ (DCIS) is confined to the ducts. Invasive disease has grown into surrounding tissue; metastatic disease has spread to distant organs. A breast cancer deposit in a lung is still breast cancer, not automatically a new lung cancer. Men can also develop breast cancer.

Risk does not explain every diagnosis

Age, inherited susceptibility, family history, prior chest radiation, hormonal exposure and alcohol can influence risk. Many patients have no strong family history. A diagnosis does not prove that a particular lifestyle choice caused the cancer; healthy habits cannot replace treatment.

Screening may find breast cancer before symptoms develop. New changes deserve assessment even after a recent normal screening result. Most breast changes are not cancer, but symptoms alone cannot reliably distinguish benign from malignant disease.

• A new breast or underarm lump, or an area of thickening.
• New nipple inversion, unexplained discharge or a persistent nipple rash.
• Dimpling, altered breast shape, persistent redness or swelling.

Rapid redness and swelling of much of the breast needs prompt assessment, including consideration of inflammatory breast cancer. Severe breathlessness or new neurological symptoms warrant urgent care rather than waiting for an online review.

Read the report on separate levels. Histology describes tissue appearance, such as invasive carcinoma of no special type or invasive lobular carcinoma. Grade describes cell appearance and proliferation. ER, PR and HER2 help select treatment. None of these alone gives the stage.

HER2-low is not HER2-positive

Keep the actual IHC score and any ISH result, not just the word negative. IHC 2+ generally needs further assessment under the testing algorithm. Low or ultralow expression can influence eligibility for particular ADCs; it does not convert every HER2-negative cancer into HER2-positive disease. Drug-selection categories are not automatically new intrinsic molecular subtypes.

Luminal A/B and other gene-expression labels should be interpreted with the method used to obtain them. A single Ki-67 cutoff cannot replace the full pathology and clinical assessment.

Confirm the tissue diagnosis

Diagnostic mammography and ultrasound evaluate suspicious findings; MRI answers selected questions rather than being automatic for everyone. Needle biopsy usually establishes the tissue diagnosis. Check that the specimen supports histology and receptor testing, and that imaging and pathology agree.

Three different meanings of a genetic test

• Inherited-risk testing usually uses blood or saliva to identify germline changes such as BRCA1/2. Results can affect treatment and relatives. A variant of uncertain significance is not a confirmed harmful variant.
• Tumor profiling identifies acquired changes that may guide treatment, especially in advanced disease. A tumor BRCA result may need separate germline assessment.
• Gene-expression recurrence assays address chemotherapy benefit in selected early HR-positive/HER2-negative cancers. Eligibility and interpretation depend on the assay, lymph nodes and menopausal status.

Choose a test because it can change a defined decision. Ask what a positive result would change and what a negative result would leave unresolved.

TNM describes the breast tumor, regional nodes and distant spread. Breast prognostic staging also considers grade and ER/PR/HER2. Clinical staging before treatment, pathological staging after initial surgery and response assessment after preoperative therapy answer related but different questions. Check when and how a stage was assigned before comparing reports.

Surgery and radiotherapy

For suitable early breast cancers, breast-conserving surgery followed by radiotherapy and mastectomy offer comparable survival. The choice also depends on tumor extent, breast size, previous radiation, inherited risk and personal preferences. A mastectomy does not automatically remove the need for radiotherapy. Sentinel lymph node assessment or other axillary management is tailored to the clinical situation; removing more lymph nodes is not always better.

Treatment before surgery

Neoadjuvant treatment may shrink a tumor, make breast conservation possible and show how the cancer responds. It is particularly important in many higher-risk HER2-positive and triple-negative cancers. The amount of invasive cancer remaining at surgery can change postoperative treatment. A complete pathological response is encouraging, but does not mean follow-up or all further treatment can stop.

Hormone receptor-positive disease

Endocrine therapy is a central treatment. Tamoxifen, aromatase inhibitors and other endocrine medicines have different uses. Menopausal status matters: an aromatase inhibitor generally requires ovarian suppression in a premenopausal patient. Chemotherapy, a CDK4/6 inhibitor or other targeted treatment may be added in defined risk groups or advanced disease. A recurrence-score test can help selected early HR-positive/HER2-negative patients assess chemotherapy benefit; it is not appropriate for every patient.

HER2-positive and triple-negative disease

HER2-positive cancers are treated with HER2-directed medicines in combinations and sequences matched to stage, prior therapy and response. For triple-negative disease, chemotherapy remains important; immunotherapy is used in particular early and advanced settings with different eligibility rules. Selected patients with an inherited BRCA mutation may benefit from a PARP inhibitor. A drug used after recurrence should not automatically be substituted into a curative early-stage regimen.

Advanced disease: sequence matters

Metastatic treatment aims to control cancer, relieve symptoms and preserve quality of life. Decisions consider receptor results from current disease, previous treatment, the speed and sites of progression, organ function and patient priorities. Endocrine-based therapy is often appropriate for HR-positive disease, but rapidly threatening organ dysfunction may require a different approach. Brain, bone or painful local disease may also need focused treatment.

New approvals can change a treatment pathway, but the relevant question is whether the evidence applies to this cancer, at this point in treatment. The examples below describe specific US regulatory settings. Approval, guideline preference, local access and suitability for an individual patient are separate questions.

Trastuzumab deruxtecan (T-DXd)

This antibody–drug conjugate has several distinct breast cancer indications. The US label includes combination with pertuzumab as first-line treatment of unresectable or metastatic HER2-positive disease, and treatment of HR-positive, HER2-low or HER2-ultralow unresectable or metastatic disease after progression on endocrine therapy in the metastatic setting. These are not interchangeable eligibility groups. The pathology result and previous treatment must be checked. Interstitial lung disease, including potentially fatal pneumonitis, is a major safety consideration.

Sacituzumab govitecan

The US label now includes first-line treatment of unresectable locally advanced or metastatic triple-negative disease: as a single agent for adults who are not candidates for a PD-1/PD-L1 inhibitor, or with pembrolizumab for eligible PD-L1-positive disease with CPS at least 10. Separate later-line indications also exist, including a defined previously treated HR-positive/HER2-negative population. Severe neutropenia and diarrhea require active monitoring and management.

An ESR1-guided endocrine switch

Camizestrant with a CDK4/6 inhibitor received US accelerated approval for a defined HR-positive/HER2-negative advanced breast cancer setting when an ESR1 mutation emerges during aromatase inhibitor plus CDK4/6 inhibitor treatment. This involves an approved plasma test and a specific monitoring and treatment pathway; it is not a reason to change therapy on an unvalidated blood test. Continued approval depends on confirmatory evidence. Cardiac rhythm risks and drug interactions require specialist assessment.

How to assess a trial

• Ask whether the trial matches the disease subtype, treatment line and prior medicines, including previous antibody–drug conjugates.
• Check the comparison treatment, known uncertainties, travel and visit requirements, and who pays for care outside the trial.
• Trial registration or a promising response rate does not establish an approved treatment or a survival benefit.

Gedatolisib: who the option is for

Gedatolisib plus fulvestrant, with or without palbociclib, is approved in the United States for adults with HR-positive, HER2-negative locally advanced or metastatic disease without a detected PIK3CA mutation, after progression on or after at least one endocrine treatment line in the metastatic setting. The mutation requirement differs from therapies selected for PIK3CA-mutated cancer. Treatment needs mouth-care prevention and monitoring for skin reactions and high blood glucose.

Recurrence may be local, regional or distant; these situations have different goals and treatment options. When feasible and clinically appropriate, a biopsy of recurrence can confirm the diagnosis and reassess ER, PR and HER2 because results may differ from the original tumor. A new lesion is not automatically a breast cancer metastasis.

Review the full treatment history, the interval since each treatment, current symptoms and imaging together. A long period of benefit followed by limited progression may raise different options from rapid progression at several sites. Prognosis depends on the current clinical picture; a population survival percentage cannot predict one person's course.

• Discuss fertility preservation before treatments that may affect ovarian function; temporary loss of periods does not reliably establish infertility or menopause.
• Report persistent joint pain, hot flushes, vaginal symptoms or mood changes during endocrine treatment. Supportive measures or an agreed treatment adjustment can help maintain treatment.
• Discuss reconstruction, body image, sexuality and rehabilitation as part of treatment planning, with timing adapted to surgery and possible radiotherapy.
• Ask about bone health, exercise and nutrition, and cardiac monitoring when the treatment requires it. Supportive and palliative care can accompany active anticancer treatment.

Arm swelling and lymphoedema

Lymph node surgery and radiotherapy can increase lymphoedema risk. New heaviness, tightness or swelling should be assessed early; rehabilitation and a trained lymphoedema service can help. Sudden redness, warmth, pain or fever needs prompt assessment for infection or another cause.

A follow-up plan with a purpose

Follow-up after early-stage treatment generally includes symptom review, examination and breast imaging appropriate to the surgery performed. Routine body scans or tumor markers are not automatically helpful in an otherwise well person without concerning findings. Follow-up during metastatic treatment has a different purpose: assessing response, toxicity and whether the plan should change.

A useful second opinion should answer a specific question: Is the diagnosis complete? Is treatment needed before surgery? Would another test change the plan? What is the next option after progression? Bring the actual reports and images rather than only a short summary.

• Biopsy and surgical pathology, including histology, grade, ER/PR percentages, HER2 IHC and any ISH result; arrange slides or tissue access if a pathology review is needed.
• Breast and staging images with their reports, plus the most recent comparison scans.
• A treatment timeline with medicine names, dates, response, reason for stopping and important side effects.
• Genetic and molecular reports with the laboratory and test method, distinguishing blood-based inherited testing from tumor or circulating tumor DNA testing.
• Current medicines, other medical conditions, menopausal status, fertility wishes and practical priorities.