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PeeterKarihtala

Breast Cancer

Essentials

  • Worldwide, breast cancer is the most common type of cancer in women.
  • The nature of a finding, found by palpation or imaging study, is determined by core-needle biopsy.
  • The surgical procedure is most often a breast-conserving operation and a sentinel lymph node biopsy in the axilla.
  • Breast-conserving surgery is almost always followed by postoperative radiotherapy.
  • Neoadjuvant treatment oradjuvant drug treatment may consist of cytostatic chemotherapy, anti-HER2 antibody therapy or endocrine (hormone) therapy, or of combinations of these.
  • A low threshold for contact in case of new symptoms and mammography every 1-2 years are the most important things in the follow-up of a patient after breast cancer.

Epidemiology

Aetiology and risk factors

  • The exact cause of breast cancer is not known but many risk factors have been identified.
    • Early age at menarche
    • Late age of menopause
    • Nulliparity or first pregnancy when over 30 years
    • Long-term use of hormone replacement therapy with a combination of oestrogen and progestin
    • Obesity (in postmenopausal women)
    • Ionising radiation
    • Excessive alcohol consumption
  • About 5-10% are associated with an inherited predisposition to breast cancer (particularly BRCA1 and BRCA2 gene mutations) Genetic Susceptibility to Breast Cancer.
  • Factors lowering the risk of breast cancer

Symptoms

  • A painless lump in the breast (in about 80% of the patients)
  • Puckering of skin or nipple inversion
  • Eczematous skin changes near the nipple (Paget's disease, picture 1)
  • Pain, tingling or feeling of heaviness in the breast
  • An axillary lump
  • Symptoms of metastatic spread
  • Discharge from the nipple (seldom)

Diagnosis Screening for Breast Cancer with Mammography, Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer

  • Triple assessment
    • Clinical examination of the breast
    • Imaging studies (mammography and other supplementing methods)
    • Core needle biopsy
  • The abnormality may be followed up if all the above methods are suggestive of a benign lesion. If the nature of the lesion remains unclear, it is surgically removed.
  • Mammography is the imaging method of choice.
  • Find out about local screening policy and practices for breast cancer.
  • The imaging tools supplementing mammography are ultrasonography and magnification mammography, in special cases galactography (examination of nipple discharge) and magnetic resonance imaging (MRI).
  • The sensitivity of mammography is better in older women than in younger women whose breast tissue is denser.
  • It is often possible to use ultrasonography to distinguish cysts from solid lesions detected by mammography.
  • A core needle biopsy is taken from the breast abnormality under ultrasound guidance. A needle biopsy should also be taken from any suspicious axillary lymph nodes.
  • Differential diagnosis should take into account e.g. benign fibrocystic changes Clinical Breast Examination: Lump, Pain and Benign Changes.
  • In primary diagnostics, laboratory tests and further imaging investigations are not beneficial unless metastases are suspected (e.g. cancer that has spread to the armpit or if the patient has symptoms)
  • The diagnosis of breast cancer should be confirmed in primary care before the patient is referred to a specialist.

Histology

  • The main histological types are invasive breast carcinoma of no special type(ductal carcinoma) and lobular carcinoma. Inflammatory carcinoma is a clinical diagnosis of cancer that grows into the lymphatic system, not a separate histological type.
    • Of invasive carcinomas, about 70-80% are invasive breast carcinomas of no special type (ductal carcinomas) and 10-15% are lobular carcinomas.
    • Ductal carcinoma in situ (DCIS) is a precancerous lesion of an invasive cancer.
    • Lobular carcinoma in situ (LCIS) is not an actual precancerous lesion but is suggestive of an increased risk of invasive cancer.
  • Rarer histological subtypes are, for example, tubular, medullary and mucinous carcinoma as well as Paget's disease of the nipple (picture 1).

Surgical treatment Prophylactic Mastectomy for the Prevention of Breast Cancer, Breast-Conserving Surgery Vs Mastectomy in Early-Stage Breast Cancer, Oncoplastic Breastconserving Surgery for Women with Primary Breast Cancer, Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer

  • Breast-conserving surgery is always applied to remove the tumour, provided that negative margins can be achieved.
  • Sentinel lymph node examination Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer is both a diagnostic and therapeutic procedure.
    • To the extent possible, axillary lymph node dissection (clearance) is nowadays avoided, even if there would be a macrometastasis in a sentinel lymph node. In specific cases (e.g. preoperatively verified lymph node metastasizing), however, axillary dissection is performed.
    • In some cases, the sentinel lymph node biopsy may also be omitted.
  • Breast reconstruction may either be carried out immediately or it may be delayed; see below.

Early postoperative complications

  • The operated area often has swelling of the skin and tissue fluid collected in the wound cavity. Swelling and erythema do not always indicate and infection.
  • A seroma (a collection of tissue fluid) can be drained in primary care via a sterile needle aspiration (video Aspiration of Postmastectomy Seroma).
  • Aspirating or draining an extensive haematoma may be warranted.
  • Postoperatively, there is often stiffness and tightness in the shoulder and armpit areas. When the arm is lifted, linear streaks causing tightness may be felt and seen. The condition is managed by stretching.
  • Pain, tingling, and numbness in the armpit and along the upper arm are caused by severing or stretching of an intercostobrachial nerve during the surgery. If the condition is not improved by self-managed exercises, the patient is referred to a physiotherapist.

Oncological adjuvant treatment Platinum Containing Regimens for Triple-Negative Breast Cancer, Radiotherapy and Surgery in Early Breast Cancer, Post-Operative Radiotherapy for Ductal Carcinoma in Situ of the Breast, Breast-Conserving Surgery Vs Mastectomy in Early-Stage Breast Cancer, Taxanes for Adjuvant Treatment of Early Breast Cancer, Combined Chemo-Endocrine Adjuvant Therapy for Patients with Operable Breast Cancer, Trastuzumab Containing Regimens for Early Breast Cancer, Tamoxifen Vs Aromatase Inhibitors in Premenopausal Early Breast Cancer, Aromatase Inhibitors Vs. Tamoxifen in Postmenopausal Women with Early Breast Cancer, Ovarian Suppression for Adjuvant Treatment of Hormone Receptor-Positive Early Breast Cancer

  • Neoadjuvant therapy denotes treatment, usually sytostatic therapy, given prior to surgery. The efficacy of neoadjuvant therapy is similar to that of postoperative treatment, i.e. adjuvant therapy. Neoadjuvant therapy is used especially in breast cancer with axillary lymph node spread and rapid growth.
  • Postoperative radiotherapy is almost always given after breast-conserving surgery. After mastectomy, the need for radiotherapy is based on the size of the tumour and the axillary lymph node status.
  • Adjuvant drug therapy may consist of chemotherapy, anti-HER2 antibody therapy or endocrine (hormone) therapy, CDK4/6 inhibitors abemaciclibor ribociclib, PARP inhibitor Parp (Poly Adpribose Polymerase) Inhibitors for Locally Advanced or Metastatic Breast Cancerolaparib, bisphosphonates or combinations of these. The choice of adjuvant drug therapy is based on the risk of recurrence, age of the patient and the biological subtype of the tumour, which is defined by e.g. the expression of oestrogen and progesterone receptors and by HER2 gene expression.
  • Prognostic factors associated with a higher risk of recurrence and the existence of micro-metastatic disease are: tumour size more than 2 cm, axillary lymph node involvement, poor histological grade (III), oestrogen- and progesterone receptor negativity and HER2 positivity.
  • Therapy of hormone receptor positive cancer with moderate to high risk of recurrence consists of anthracycline- and taxane-containing chemotherapy regimens and endocrine therapy.
  • Courses of chemotherapy are usually administered postoperatively in 6 cycles with 3-week intervals (for 4 months).
  • In HER2 positive breast cancer, antibody treatment is given concomitantly with adjuvant chemotherapy.
  • The duration of endocrine therapy is 5-10 years. In cancer with high risk of recurrence, the duration is 10 years. In premenopausal patients, tamoxifen is used Tamoxifen Vs Aromatase Inhibitors in Premenopausal Early Breast Cancer and in postmenopausal patients either aromatase inhibitors Aromatase Inhibitors Vs. Tamoxifen in Postmenopausal Women with Early Breast Cancer (letrozole, anastrozole or exemestane) or tamoxifen is used. LHRG analogue therapy, combined with an aromatase inhibitor or tamoxifen, may be used in premenopausal patients if the recurrence risk is high.
  • If the patient requires all the adjuvant therapies, the treatment is started with chemotherapy and continued with radiotherapy. Endocrine therapy is started in association with radiotherapy or immediately after it.

Breast reconstruction

  • When mastectomy is to be performed, the possibility of breast reconstruction is discussed with the patient.
  • Breast reconstruction may be performed in association with the operation (immediate reconstruction) or later (delayed reconstruction).
  • Usually, either an abdominal or a dorsal flap (picture 3), prosthesis, fat transfer or some combination of these is used in breast reconstruction.
  • If breast-conserving surgery is performed, the operated breast can be shaped with plastic surgery techniques. If necessary, the other breast can be made smaller in order to achieve a symmetrical and well-proportioned result (oncoplastic surgery).

Rehabilitation Exercise for Women Receiving Therapy for Breast Cancer, Physical Therapist Management of Lymphoedema Following Treatment for Breast Cancer, Psychological Interventions for Women with Breast Cancer

  • After surgery, a physiotherapist should advise the patient how to stretch and exercise the upper limb and shoulder joint. The patient will then continue to do the exercises daily. Exercises will reduce the risk of oedema in the arm as well as tightening of the scar tissue, particularly after lymph node dissection.
  • Long-term oedema in the affected arm can be reduced with :
  • Find out about local policies and practices concerning breast prosthesis and compression sleeves.
  • After mastectomy, a breast prosthesis should also be worn at home to ensure that the weight exerted on the shoulders is symmetrical.
  • If the patient loses her hair due to postoperative chemotherapy or chemotherapy given to treat metastases, the purchase of a wig is usually reimbursed to the patient, depending on local protocols.
  • Adjustment training courses as well as recreational and support activities are available according to the local arrangements and resources.
  • If the patient requires both chemotherapy and radiotherapy after surgery, the sick leave may last all in all for more than half a year. Breast cancer surgery and the adjuvant therapies do usually not cause prolonged inability to work after this.

Follow-up Mammography for Follow-Up in Breast Cancer

  • The prognosis of non-metastatic breast cancer is usually good. The 10-year relative survival is about 90%. On the other hand, also late recurrences occur. In general, more aggressive breast cancers recur at an earlier stage.
  • The aim is to identify and treat any adverse effects caused by the primary treatment, detect contralateral breast cancer or local recurrence of the treated cancer, and support the patient's recovery by organising rehabilitation and psychosocial support.
  • As adjuvant treatment is given to patients with an increasingly lower risk of recurrence and as new drug therapies are being introduced, it is more important than ever that attention is paid to long-term adverse effects in the follow-up.
  • The most common adverse effects of endocrine therapy are hot flushes, which in some patients are relieved by e.g. (es)citalopram or venlafaxine; see tableT1. The NK-3 blocker fezolinetetan has not been studied in breast cancer survivors.
  • Patient's follow-up can be carried out in primary care, in accordance with instructions supplied by the specialized care.
    • Follow-up can be carried out as fully symptom-based, as regular appointments or as a combination of both.
      • Regular follow-up appointments have not been proven beneficial.
    • During a possible appointment, the patient should be asked about possible symptoms.
    • In an asymptomatic patient, there is no need to carry out imaging or laboratory studies for the detection of possible metastases. Pain and worsening general condition may be signs of metastatic spread.
    • Breasts, the surgical site as well as lymph nodes in the upper body should be palpated. The skin of the upper trunk as well as the range of motion of the shoulder joint in the affected side should also be checked.
    • Mammography is performed at 1-2-year intervals The mammography is supplemented when necessary with ultrasonography of the breasts and the operated area at a radiologist's discretion. Screening imaging can be utilized in the follow-up.
    • Mammography follow-up should be continued until the patient is about 80 years old, or as long as her general health remains good.
    • If breast metastasis is suspected or detected, the patient should be referred to specialized care.

Non-endocrine treatment options for breast cancer patients for adverse effects of endocrine therapy and evidence on the effectiveness of treatments

TreatmentHot flushesDisorders of sexual functionWeight gainMusculoskeletal symptomsFatigue
SSRI and SNRI medications*×××oo×××o
Gabapentin, pregabalin×××oooo
Switching from one aromatase inhibitor to anotherooo××o
Vaginal moisturizerso×××ooo
Cognitive behaviour therapy×××××××××××××××
Physical trainingoo×××××××××
Acupuncture××oo×××××
Hypnosis××oooo
Yoga and mindfulness××o×××××
CYP2D6 inhibitors (e.g. duloxetine and paroxetine) are not recommended in combination with tamoxifen.
o = Insufficient data in breast cancer patients
× = May be effective (single-arm studies)
×× = Some evidence of efficacy (randomized controlled trials with small data sets)
××× = Probably effective (randomized controlled trials)
Adapted from Franzoi MA, Agostinetto E, Perachino M, et al. Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer. Lancet Oncol 2021 Jul;22(7):e303-e313. [PubMed]
Pregnancy and breast cancer
  • Surgery is possible at all stages of pregnancy.
  • Radiotherapy is contraindicated throughout pregnancy. Chemotherapy is not recommended during the first trimester of pregnancy, and some of the cytotoxic agents may also be harmful for the foetal development during later pregnancy.
  • A new pregnancy is recommended to be tried about two years after the treatment of breast cancer. Pregnancy after treatment has not been found to be a risk factor for recurrent breast cancer. Chemotherapy or radiotherapy for breast cancer has not been found to increase the risk of malformations, provided that the pregnancy starts after the treatment has been discontinued.
  • Tamoxifen is a teratogenic drug and its use should be interrupted in collaboration with an oncologist and gynaecologist if the patient wishes to become pregnant during tamoxifen treatment.
  • After breast-conserving surgery, it usually is not possible to breast feed from the operated breast. Milk secretion of the contralateral breast is not affected by the treatments.

Treatment of menopausal symptoms

Treatment of recurrent and advanced cancer Taxane Containing Regimens for Metastatic Breast Cancer, Antitumour Antibiotic Containing Regimens for Metastatic Breast Cancer, Aromatase Inhibitors for Treatment of Advanced Breast Cancer in Postmenopausal Women, Fulvestrant for Hormone-Sensitive Metastatic Breast Cancer, Progestogens and other Hormone Therapies in Women with Breast Cancer and Bone Metastasis, Bisphosphonates in Breast Cancer, Platinum Containing Regimens for Triple-Negative Breast Cancer, Cytotoxic and Hormonal Treatment for Metastatic Breast Cancer, Parp (Poly Adpribose Polymerase) Inhibitors for Locally Advanced or Metastatic Breast Cancer

    References

    • Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2024;35(2):159-182 [PubMed]
    • Gennari A, André F, Barrios CH, et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol 2021;32(12):1475-1495. [PubMed]http://www.annalsofoncology.org/article/S0923-7534(21)04498-7/fulltext
    • Loibl S, Poortmans P, Morrow M, et al. Breast cancer. Lancet 2021;397(10286):1750-1769. [PubMed]