Bibliothèque NCBI. Un service de la Bibliothèque nationale de médecine, Instituts nationaux de la santé.

StatPerles [Internet]. Île au Trésor (FL) : StatPearls Publishing ; 2026 janvier-.

Cancer du sein
Gopal Menon ; Fadi M. Alkabban ; Troy Ferguson .

Informations sur l'auteur et ses affiliations

Dernière mise à jour : 25 février 2024 .

Activité de formation continue

Le cancer du sein est le cancer le plus fréquemment diagnostiqué chez les femmes, représentant
plus d'un nouveau cas sur dix chaque année, et constitue la deuxième cause de mortalité par
cancer chez les femmes dans le monde. Les facteurs de risque du cancer du sein sont bien établis
et leur réduction joue un rôle essentiel dans la diminution de son incidence. Le cancer du sein
évolue généralement de façon asymptomatique et est le plus souvent découvert lors d'un
dépistage systématique dans les pays occidentaux. En l'absence de dépistage, il est souvent
détecté par la palpation d'une masse au sein. La chirurgie, la radiothérapie, la chimiothérapie et
l'immunothérapie sont utilisées en association pour traiter le cancer du sein, en fonction du stade
et du type de tumeur. Les progrès réalisés dans ces modalités de traitement ont permis
d'améliorer significativement la survie globale et les résultats rapportés par les patientes.

Cette activité destinée aux professionnels de la santé vise à renforcer leurs compétences en
matière de prise en charge du cancer du sein, en leur fournissant des connaissances, des
compétences et des stratégies actualisées pour un dépistage précoce, des interventions efficaces
et une meilleure coordination des soins, ce qui permet d'obtenir de meilleurs résultats pour les
patientes et de réduire la morbidité.

Objectifs :

Identifier les facteurs de risque du cancer du sein.

Différencier les différents types de cancer du sein.

Comparez les options de traitement recommandées pour le cancer du sein.

Élaborer des stratégies avec les membres de l'équipe interprofessionnelle afin d'améliorer
les soins aux patients et d'optimiser les résultats pour les patientes atteintes d'un cancer du
sein.

Accédez gratuitement à des questions à choix multiples sur ce sujet.

Introduction
Le cancer du sein est le cancer le plus fréquemment diagnostiqué chez les femmes et la deuxième
cause de mortalité par cancer chez les femmes dans le monde. [1] Les seins sont des glandes
paires de taille et de densité variables, situées superficiellement au muscle grand pectoral. Ils
contiennent des cellules productrices de lait organisées en lobules ; plusieurs lobules sont
regroupés en lobes, avec du tissu adipeux intercalé. Le lait et les autres sécrétions sont produits
dans des acini et expulsés par les canaux galactophores qui débouchent au niveau du mamelon.
Les seins sont ancrés au fascia musculaire sous-jacent par les ligaments de Cooper, qui assurent
leur soutien. [2]

Le cancer du sein se développe le plus souvent dans l'épithélium canalaire (carcinome canalaire),
mais peut également se développer dans les lobules mammaires (carcinome lobulaire). Plusieurs
facteurs de risque du cancer du sein sont bien décrits. Dans les pays occidentaux, les programmes
de dépistage ont permis d'identifier la plupart des cancers du sein grâce au dépistage, plutôt que
par la détection de symptômes. Cependant, dans une grande partie des pays en développement,
une masse mammaire ou un écoulement anormal du mamelon constitue souvent le premier
symptôme. [3] Le diagnostic du cancer du sein repose sur l'examen clinique, l'imagerie
mammaire et la biopsie tissulaire. Les options thérapeutiques comprennent la chirurgie, la
chimiothérapie, la radiothérapie, l'hormonothérapie et, plus récemment, l'immunothérapie. Des
facteurs tels que l'histologie, le stade, les marqueurs tumoraux et les anomalies génétiques
orientent les décisions thérapeutiques individualisées. [1]

Étiologie
Facteurs de risque du cancer du sein

L’identification des facteurs associés à une incidence accrue de cancer du sein est importante
dans le cadre du dépistage général chez les femmes. Les facteurs de risque du cancer du sein
comprennent : [4] [5] (voir l’image : Facteurs de risque du cancer du sein).

Âge : L’incidence du cancer du sein, ajustée en fonction de l’âge, continue d’augmenter avec le
vieillissement de la population féminine.

Sexe : La plupart des cancers du sein surviennent chez les femmes.

Antécédents personnels : Des antécédents de cancer du sein augmentent la probabilité d'un

second cancer primitif dans le sein controlatéral.

Histologiques : Les anomalies histologiques diagnostiquées par biopsie mammaire constituent

une catégorie essentielle de facteurs de risque de cancer du sein. Ces anomalies comprennent le
carcinome lobulaire in situ (CLIS) et les modifications prolifératives avec atypie.

Antécédents familiaux et mutations génétiques : Les apparentés au premier degré de patientes

atteintes d’un cancer du sein présentent un risque deux à trois fois plus élevé de développer la
maladie. Les facteurs génétiques sont responsables de 5 à 10 % des cancers du sein, mais
peuvent représenter jusqu’à 25 % des cas chez les femmes de moins de 30 ans. Les gènes
BRCA1 et BRCA2 sont les principaux gènes impliqués dans l’augmentation de la prédisposition
au cancer du sein.

Reproductive: Reproductive milestones that increase a woman’s lifetime estrogen exposure are
thought to increase breast cancer risk. These include the onset of menarche before age 12, first
live childbirth after age 30 years, nulliparity, and menopause after the age of 55.

Exogenous hormone use: Therapeutic or supplemental estrogen and progesterone are taken for
various conditions, with the most common scenarios being contraception in premenopausal
women and hormone replacement therapy in postmenopausal women.

Other: Radiation, environmental exposures, obesity, and excessive alcohol consumption are
some other factors that are associated with an increased risk of breast cancer.

Epidemiology
Invasive breast cancer remains the most common cancer among women worldwide, accounting
for approximately 11.7% of new cases in 2020.[6] In the US, 1 in 8 women and 1 in 1000 men
will develop breast cancer during their lifetime.[7][8][9] The incidence rate of breast cancer
increases with age, from 1.5 cases per 100,000 in women aged 20 to 24 to a peak of 421.3 cases
per 100,000 in women aged 75 to 79; 95% of new cases occur in women aged 40 years or older.
The median age of women at the time of breast cancer diagnosis is 61 years.

A rapid increase in the incidence of breast cancer was noted until 2000, after which the incidence
began to decline. More significant decreases occur in women younger than 50 years. With early
detection and significant advances in treatment, breast cancer death rates have decreased over the
past 25 years in North America and parts of Europe. In the US, breast cancer-related mortality
dropped by 43% from 1980 to 2020. However, in many African and Asian countries (eg,
Uganda, South Korea, and India), breast cancer incidence and death rates continue to rise.
[6] Even within the US, marked disparity exists in detection and survival rates based on
socioeconomic status and race. Although the incidence is highest among non-Hispanic whites,
the mortality rate is significantly higher among African Americans. According to the American
Cancer Society (ACS), breast cancer rates among women from various racial and ethnic groups
are as follows:[10]

Non-Hispanic white: 128.1 in 100,000

African American: 124.3 in 100,000

Hispanic/Latina: 91.0 in 100,000

American Indian/Alaska Native: 91.9 in 100,000

Asian American/Pacific Islander: 88.3 in 100,000

Pathophysiology
Most breast cancer is sporadic (90%-95%), with only 5% to 10% of patients having an
identifiable genetic mutation.[11] BRCA 1 and 2 are the most common associated genetic
conditions. Invasive ductal and invasive lobular carcinoma are the most common pathologic
forms of invasive breast cancer. Carcinogenesis occurs due to a complex interplay of genetic and
environmental risk factors, hormonal influences, and patient-related factors. The pathogenesis,
treatment, and prognosis are closely associated with the following molecular subtypes of breast
cancer:

Luminal A: Hormone receptor-positive, human epidermal growth factor receptor (HER)-2

negative

Luminal B: Hormone receptor-positive, HER-2 positive

Basal-like: Hormone receptor and HER-2 negative

HER-enriched: HER-2 positive, hormone receptor-negative

Hormone receptor-positive tumors (ie, luminal A and B) tend to be less aggressive, with
improved survival rates.[12] HER-2 enriched tumors are more aggressive, with a poor prognosis
without targeted therapy. In the era of targeted anti-HER therapy (eg, trastuzumab), the paradigm
has shifted.[13] Basal-like tumors are negative for the molecular markers and tend to have a
worse prognosis with poor survival rates.[14]

Histopathology
Invasive breast cancer is characterized by the invasion of neoplastic cells beyond the basement
membrane that can be morphologically varied, with several subtypes described. All specimens
should be tested for hormone receptors (ie, estrogen and progesterone) and HER-2 receptors. (see
Image. Breast Estrogen Receptor Staining) Other critical components assessed on the
histopathologic exam include tumor grade, pleiomorphism, Ki-67 index, morphology, tumor
necrosis, multifocality, and precancerous lesions. The following are the most common histologic
types of invasive breast cancer.

Ductal adenocarcinoma: This histologic type comprises 50% to 75% of all invasive breast
cancers. Clinically, these tumors are often felt as a breast mass secondary to a significant fibrotic
reaction. Microscopically, the lesion arises in the terminal duct-lobular unit with abnormal
epithelial cells with varying degrees of atypia. These cells invade the basement membrane.
However, there are no pathognomonic histologic features of invasive ductal carcinoma.[1] (see
Image. Invasive Ductal Carcinoma).

Lobular carcinoma: Invasive lobular cancer makes up 10% to 15% of breast cancer and tends to
permeate the breast in a single-file nature. This results in tumors that typically remain clinically
occult, escaping detection on mammography or physical examination until the disease becomes
extensive. A discrete mass is seldom palpated. Multifocal tumors and bilateral disease are more
common with invasive lobular carcinoma. Characteristically, these tumors stain negative for E-
cadherin.[15] (see Image. Pleomorphic Lobular Breast Carcinoma).

Mucinous carcinoma: Also known as colloid carcinomas, these tumors, which make up 2% to
5% of breast cancers, are well-demarcated in older women, typically characterized by mucin
production.[16]

Tubular carcinoma: Microscopically characterized by infiltrating cells with minimal atypia that
form small glands and tubules, 1% to 2% of breast cancers are among this subtype.[16]

Medullary carcinoma: These aggressive tumors are poorly differentiated and seen more
commonly in BRCA mutant and younger patients.[17]

History and Physical

A periodic review of patient history for breast cancer risk assessment is recommended by the
American College of Obstetricians and Gynecologists (ACOG).[18] Clinicians can use online
assessment tools to help calculate a patient's breast cancer risk. Most breast cancer patients are
asymptomatic, and lesions are discovered during routine breast examination or screening
mammography. With increasing size, the patient may notice a palpable lump. Breast pain is an
unusual symptom that happens 5% of the time.[19] More advanced disease may present with
symptoms including peau d'orange, frank ulceration, axillary lymphadenopathy, or signs of
distant metastasis. Inflammatory breast cancer, an advanced form of breast cancer, may have
clinical features similar to breast abscess (eg, swelling, redness, and other local signs of
inflammation).[20] (see Image. Breast Cancer Axillary Lymphadenopathy)

A thorough physical exam is a vital part of the clinical assessment for breast cancer. Both breasts
must be examined in the sitting, standing, and supine positions, with the arm abducted, extended,
and externally rotated. Palpation Overlying skin changes, nipple discharge, edema, peau
d'orange, and ulceration should be noted. (see Image. Clinical Signs of Breast Carcinoma).
Careful palpation of the regional lymph node basins for lymphadenopathy is also essential.
Although some societies (eg, American Cancer Society) no longer recommend routine clinical
breast examinations in asymptomatic, low-risk women as it has not been found to have a
significant benefit, ACOG states that routine clinical breast examinations may be offered to these
women, though not required. Furthermore, ACOG recommends an interval of every 1 to 3 years
for women aged 25 to 39 years, and every year for women >40 years is appropriate if a screening
breast examination is performed. However, a clinical breast examination should always be done
for high-risk women and symptomatic women.[18] See StatPearls' companion topic, "Breast
Examination Techniques," for additional information on clinical breast exams.[21]

Evaluation
Diagnostic Breast Imaging

Mammography is the most commonly used modality for screening and diagnosis of breast
cancer.[22] Abnormal findings on mammography include mass lesions, calcifications, or
architectural distortion. When identified on screening mammography, diagnostic mammography,
which utilizes higher quality imaging with several views, is indicated. Mammography is of
limited utility in patients with dense breasts, in younger patients, and in those who cannot
tolerate the breast compression that is required. Breast ultrasound or magnetic resonance imaging
(MRI) with contrast may be utilized in such cases. Breast ultrasound is similar in sensitivity to
mammography and can be used to obtain image-guided biopsy. Though MRI is the most
sensitive imaging study, it is time-consuming, has limited availability, and is expensive.
[23] Indications for MRI include axillary lymph node disease and an occult primary malignancy,
Paget disease, multifocal or bilateral cancers, neoadjuvant chemotherapy treatment response
assessment, and high-risk patient screening.[24] (see Image. Breast Mammogram)

Breast imaging findings are classified by their Breast Imaging Reporting and Data System (BI-
RADS) category, which correlates imaging findings with their probability of underlying
malignancy and recommends a broad treatment strategy. The BI-RADS categories range from 0
to 6.[25]

Table

Tissue Biopsy

Once a suspicious lesion is identified, tissue biopsy with stereotactic core needle biopsy is
performed with imaging guidance.[26][27][28] Core needle biopsy is superior to fine needle
aspiration and should be performed whenever possible.[29] In patients with clinically positive
regional lymph nodes, an ultrasound-guided core needle biopsy is performed. Radiographically
identifiable markers should be placed during the biopsy to mark the site in both the primary
cancer and the lymph node basin to help identify and localize the lesion later. Breast tissue must
be sent for a pathologic exam, including hormonal and Herceptin receptor testing.

Staging Imaging

Routine laboratory investigations and imaging for systemic disease are not recommended for
operable breast cancer in the absence of symptoms. If associated symptoms are present, an MRI
brain, chest CT scan, bone scan, or CT of the abdomen and pelvis may be performed as
indicated. Baseline complete blood count and comprehensive metabolic panel, including liver
function tests, are indicated if neoadjuvant chemotherapy is planned. For clinically advanced
breast carcinoma (eg, inflammatory breast cancer, chest wall or skin involvement, and bulky
axillary lymphadenopathy), a chest, abdomen, and pelvis CT along with a bone scan or an FDG-
PET scan is often used.[30]

Treatment / Management
Breast cancer treatment is nuanced and based on various factors, including the disease stage,
pathology, patient preference, and available resources. In general, breast cancer management
approaches are divided into early breast cancer, locally advanced breast cancer, and metastatic
breast cancer treatment.[30]

Early Breast Cancer

Early breast cancer includes tumors <5 cm in size without clinically positive lymph nodes.
Treatment involves surgery, chemotherapy, radiation, and hormonal therapy, depending on the
stage and molecular profile.[30] The modalities used include:

Surgical treatment: Options to excise the primary tumor include breast conservation
surgery (eg, partial mastectomy or lumpectomy) or a total mastectomy.

Axillary lymph node management: Sentinel lymph node biopsy is performed during the
operation. Without extranodal extension, no further axillary surgery is required if 2 to 3
axillary lymph nodes are microscopically positive. A completion axillary dissection or
axillary radiation is indicated in patients with >3 positive lymph nodes or extranodal
 extension.

Chemotherapy: Systemic chemotherapy is indicated based on the final stage and the
tumor's molecular profile.

In hormone receptor-positive tumors, the decision to initiate chemotherapy is based

on risk stratification using genomic analysis of the primary using commercially
available kits (eg, Oncotype Dx). High-risk patients benefit from chemotherapy in
addition to hormonal therapy.

All HER2-positive patients with tumors >1 cm should receive anti-HER2-directed

therapy.

All triple-negative patients with tumors > 1 cm should receive systemic

chemotherapy.

Radiation: Patients undergoing breast conservation surgery (BCS) must receive radiation
to the breast with a boost to the tumor bed to reduce local recurrence. Patients who
undergo mastectomy do not need breast radiation, except in certain circumstances (eg, >5
cm tumor, chest wall invasion, skin involvement, multifocal tumor, ≥4 positive nodes).

Hormonal therapy: Anti-estrogen or aromatase inhibitor therapy is indicated in all

hormone receptor-positive patients.

Up-front chemotherapy (ie, neoadjuvant therapy) has been increasingly used in early-stage triple-
negative and HER2-positive tumors. Delivering the chemotherapy up-front has several
advantages, including allowing response assessment, a greater likelihood of completing
chemotherapy, and an increased likelihood of breast conservation therapy; therefore, clinicians
will likely use this strategy more extensively.[31][32]

Locally Advanced Breast Cancer (LABC)

Locally advanced breast cancer (LABC) primarily consists of tumors larger than 5 cm or those
with clinically positive lymph nodes. Most patients with LABC will receive some form of
neoadjuvant therapy, with adjunct surgery and radiation therapy. Patients with LABC typically
undergo a breast MRI at baseline. The primary tumor and the involved lymph nodes must have
radiographically detectable markers placed before initiation of chemotherapy, as tumors can
shrink and disappear after therapy.[30]

Chemotherapy regimens vary based on the tumor pathology (eg, hormone receptor-positive,
HER2-positive, or triple-negative), the patient's age and physical status, and locally available
resources. The goals of upfront chemotherapy are to reduce the size of the primary, eradicate
micrometastatic disease, and assess disease biology based on the responsiveness of the tumor to
chemotherapy. After completion of the chemotherapy regimen, breast and axillary imaging are
repeated to assess response to chemotherapy and determine further management, including:

Surgical treatment: Options to excise the primary tumor include BCS or a total
mastectomy. Contraindications to BCS include large tumors, chest wall or skin
involvement, multifocal disease, inability to receive radiation, and large tumor size to
breast size ratio.

Axillary lymph node management: In patients with a clinically positive axilla at

diagnosis, an axillary dissection is always performed, regardless of the response of the
tumor to neoadjuvant chemotherapy. In patients with a clinically negative axilla, sentinel
lymph node biopsy is performed at the time of surgery. At least 3 lymph nodes should be
harvested using a dual-tracer technique. Patients with residual disease should undergo a
completion axillary dissection or axillary radiation.
 Systemic chemotherapy: Patients with residual disease after systemic chemotherapy may
benefit from additional chemotherapy based on the molecular characteristics.

Radiation therapy: The indications for radiation are similar to BCS.

Hormonal therapy: Anti-estrogen or aromatase inhibitor therapy is indicated in all

hormone receptor-positive patients.

Metastatic Breast Cancer

Metastatic breast cancer is managed primarily with systemic therapy. Chemotherapy, targeted
therapy, immunotherapy, and hormonal therapy are all options, depending on the molecular
profile and patient fitness. Palliative radiation may be used in controlling bulky primary disease
and metastases to the brain, bone, and lung. Surgery is not recommended except for symptom
control and palliative therapy.[33]

Differential Diagnosis
The differential diagnosis for breast cancer includes the following:

Mastitis or breast abscess: Mastitis can be confused with inflammatory breast cancer.
Inflammation or cellulitis that does not respond to antibiotics should be evaluated further.

Fat necrosis: Traumatic fat necrosis can harden and present as a mass that mimics breast
cancer.

Fibroadenoma: Fibroadenomas >2 cm are typically excised to rule out coexisting breast
cancer.

Surgical Oncology
Surgery plays a central role in managing breast cancer.[30] With the increased use of highly
effective chemotherapy and targeted therapy, operations have become less extensive and morbid,
while survival has improved. In current practice, surgery helps manage the primary tumor and
provides essential staging information. BCS can be performed in most patients with tumors <5
cm, provided that the breast is large enough for a cosmetic result. Mastectomy is indicated in
large primary tumors, tumors invading the skin or chest wall, multifocal cancers, inflammatory
breast cancer, and in patients who are unable to have radiation. Sentinel lymph node biopsy is a
vital staging procedure in patients with a clinically negative axilla. Those with 1 to 3 positive
lymph nodes on sentinel node biopsy and without gross extranodal extension can safely avoid
axillary lymph node dissection. Patients with clinically positive axillary nodes typically require
an axillary lymph node dissection.[34] The following are the primary operations performed for
breast cancer and in the axilla.

Partial Mastectomy or Lumpectomy

Partial mastectomy or lumpectomy involves the excision of a portion of the breast tissue with a
margin of healthy tissue.[35] The incision can vary based on the location of the tumor and the
desired cosmesis. Typically incisions are circumareolar, radial, or along the breast skin crease.
Partial mastectomy is the centerpiece of BCS, allowing for the conservation of most of the
breast. The cosmetic results depend on the amount of breast tissue removed compared to the
remaining breast tissue and the nipple preservation. For nonpalpable lesions, the lesion must be
localized preoperatively, usually with a wire or radioactive seed, to ensure the removal of the
entire tumor.

Simple Mastectomy and Nipple-sparing Mastectomy

Simple mastectomy involves excision of the entire breast and nipple-areola complex.[34] The
underlying pectoralis major fascia is removed as well. The amount of skin preserved can vary
based on whether reconstruction is planned and on the type of reconstruction. A nipple-sparing
mastectomy is a relatively recent modification of the simple mastectomy in which the nipple-
areolar complex is spared, and the breast tissue is excised through a small circumareolar incision.
The cosmetic results of reconstruction are superior to a conventional mastectomy, with a slightly
increased but acceptably poorer oncologic outcome.

Modified Radical Mastectomy

Modified radical mastectomy combines the simple mastectomy technique with axillary lymph
node dissection. The mastectomy incision is usually extended for the axillary contents to be
removed. Radical mastectomy, which includes the removal of the pectoral muscles and sacrifice
of the nerves, is seldom performed.

Axillary Sentinel Lymph Node Biopsy and Axillary Lymph Node Dissection

The axillary lymph nodes drain much of the ipsilateral breast and are divided into 3 levels by the
pectoralis minor muscle. A radiotracer or blue dye is injected near the primary, and 1 to 3 lymph
nodes in the axilla that have the highest uptake of radiotracer or are blue are excised. When done
with a lumpectomy, the same incision can sometimes be used, or a separate incision at the
axillary hairline may be required. Axillary lymph node dissection involves the removal of all the
fibrofatty and lymphoid tissue in levels 2 and 3, with preservation of the long thoracic nerve and
thoracodorsal nerve.[36][37]

Radiation Oncology
Radiation therapy has a significant role in local disease control, primarily in the adjuvant setting,
but may also be used for palliative therapy. In early-stage breast cancer, adjuvant radiotherapy
has been shown to reduce the risk of breast recurrent disease by approximately 50%.[38]
[39] While adjuvant radiotherapy in early-stage breast cancer has not been shown to improve
overall survival, it is an essential part of the breast conservation approach as radiotherapy
reduces the risk of recurrence and the need for additional surgery. Modalities to deliver
adjuvant radiotherapy include external beam radiation, brachytherapy, or a combination.[40][41]

Radiation Therapy Delivery Techniques

Accelerated Partial Breast Irradiation

A select number of patients may qualify for Accelerated Partial Breast Irradiation (APBI). The
American Society of Radiation Oncologists (ASTRO) appropriateness guidelines consist of
suitable, cautionary, and unsuitable candidates for this treatment.[42] APBI may be delivered
using surgically implantable single or multi-channel channel catheter devices. These implants
rely on an Ir-192 HDR afterloader to deliver conformal radiotherapy via brachytherapy. (See
StatPearls' companion topic, "Brachytherapy," for additional information.) Alternatively, APBI
may be delivered using external beam radiotherapy. In this case, an implantable device is
unnecessary, but surgical clips, coils, or 3D implantable markers may be used to delineate the
surgical cavity for external beam radiotherapy planning. The dosing is 34 to 38.5 over 10
fractions delivered twice a day. The advantage of APBI is that it can be delivered over 1 week as
opposed to 3 to 6 weeks with whole breast radiation. However, if the patient opts for APBI
delivered via catheter, there may be additional delays as the patient would likely need to return
for further surgery. In terms of outcomes, the 10-year cumulative incidence of breast cancer
recurrence for patients treated with APBI was 4.6%.[43]

Whole Breast Radiation

Whole breast radiotherapy (WBRT) is a well-studied technique employed in patients with early-
stage breast cancer and continues to be the mainstay treatment for many patients. WBRT is
delivered in the adjuvant setting either after breast-conserving surgery or after the completion of
chemotherapy. The treatment technique is designed to cover all visible breast tissue on CT
simulation. This can be safely planned and delivered using a 3D conformal plan. The ipsilateral
lung and heart doses are the most important to consider when planning these cases. Dosing varies
from 40.05 to 50.4 Gy in 15 to 25 fractions. The 10-year ipsilateral breast recurrence rate in these
patients is approximately 3.9%.[43]

An additional radiation dose, a boost, may be given to the surgical cavity upon completion of
whole breast radiation. Several randomized trials have demonstrated an improvement with local
control. Early-stage breast cancer patients who received a 10 Gy boost to the surgical cavity after
whole breast radiation had a 5-year local recurrence rate of 3.6% compared to 4.5% without a
boost. The EORTC demonstrated a 10-year local control rate of 6% versus 10% without a boost.
[44] The benefit of a radiation boost appears to be confined to younger women aged <60 years.
[44] The dosing ranges from 10 to 16 Gy. The boost is not without a cost, as there is a risk of
breast fibrosis that may impact cosmesis. The EORTC trial found a 4.4% rate of severe fibrosis
in patients receiving a boost compared to 1.6%.[44]

Post-Mastectomy Radiation

Post-mastectomy radiation (PMRT) is indicated in patients with nodal disease after axillary
staging, positive margins, and in patients with primary breast tumors >5 cm. PMRT may also be
considered in patients with high-risk pathologic features, including central or medial tumors ≥2
cm with either lymphovascular invasion, grade 3, or hormone receptor-negative. Coverage
includes the chest wall with or without regional lymphatics. PMRT has been extensively studied
in several prospective trials. The Danish 82bc trials investigated the benefit of PMRT in
premenopausal and postmenopausal high-risk patients (ie, >5 cm, locally invasive, or node-
positive). The study demonstrated long-term breast cancer mortality, locoregional recurrence,
and overall survival benefits.[45] The 30-year follow-up data continues to show overall survival
(19% versus 14%), breast cancer mortality (56% versus 67%), and locoregional recurrence (9%
versus 37%) benefits.[45]

Comprehensive Nodal Irradiation

Comprehensive nodal radiation (CNI) covers all lymphatics draining the breast and chest wall,
which consists of the levels I to III axilla, supraclavicular nodes, and internal mammary nodes.
CNI can be incorporated into WBRT or PMRT and is indicated in node-positive patients, either
from a sentinel node biopsy or axillary dissection. In patients undergoing an axillary dissection,
the radiotherapy typically includes undissected areas and areas at risk for nodal involvement.
CNI is technically more challenging than WBRT alone, requiring additional fields (ie, 3 or 4
field plans). CNI also increases the dose to uninvolved structures such as the lungs and heart.
Meeting heart constraints may become especially challenging when treating the left breast.
Certain techniques such as deep inspiratory breath hold (DIBH) or intensity-modulated radiation
therapy (IMRT) may be helpful in these circumstances to minimize the amount of dose received
by these structures. CNI has been prospectively compared to axillary dissections in patients with
1 to 3 nodes positive and was found to have similar rates of axillary control (0.93% versus
1.82%).[46] In addition, CNI has also been shown to improve 10-year disease-free survival (77%
versus 82%) without an improvement in overall survival in high-risk patients.[47] Using CNI
may also increase the risk of lymphedema as the regional lymphatics are radiated, making it
more difficult to drain the breast and upper extremity. The additional dose to the lung may also
increase the risk of radiation pneumonitis.

Intensity-Modulated Radiation Therapy

Breast intensity-modulated radiation therapy (IMRT) may be used as an alternative to

conventional 3D planning in certain circumstances, such as failure to meet heart dose constraints,
which is common, especially in patients with left-sided disease. Several prospective randomized
trials have compared 3D or 2D planning to IMRT. They have consistently demonstrated that
grade 2 or higher radiation dermatitis was significantly lower with IMRT than with 3D.[48][49]
No differences in recurrence or survival were noted.

Radiation Therapy Complications

Cardiac toxicity

The risk of major coronary events as a long-term complication of breast irradiation has been well
documented. Exposure of the coronary arteries may lead to accelerated atherosclerosis of the
vessel, resulting in significant coronary events years after radiotherapy. A population case-
control study demonstrated that the risk increases linearly with the dose to the heart, increasing
the relative risk by 7.4% per gray without an apparent threshold.[50] Women with preexisting
cardiac risk factors may have an even higher risk.[50]

Pneumonitis

The development of radiation pneumonitis in patients receiving adjuvant radiotherapy for breast
cancer ranges from 0.8% to 2.9%.[51] Radiation pneumonitis has been documented in patients
up to 1-year post-radiation and can require steroid treatment, oxygen therapy, and, in severe
cases, intubation. The risk of pneumonitis increases with the volume of lung irradiated. Patients
receiving comprehensive nodal RT are known to have higher rates of pneumonitis. The MA.20
study reported pneumonitis in 1.2% of their patients receiving regional nodal RT versus 0.2% in
those treated to the breast only.[47] Concurrent use of taxanes such as paclitaxel, common in
modern breast cancer chemotherapy regimens, may substantially increase the risk of pneumonitis
in patients receiving radiation.[52] The most effective preventative measure is meticulous
radiation planning and adherence to published lung dose constraints.

Breast fibrosis

Fibrotic changes in the breast are relatively common among patients receiving adjuvant
radiotherapy. Onset is typically 4 to 12 months posttreatment, and the symptoms include breast
shrinkage, hardening, pain, and poor wound healing. These changes can significantly affect
cosmesis. The incidence in the literature ranges from 10% to 15%.[53] However, this risk of
moderate to severe fibrosis may be influenced by several risk factors such as whole breast
radiation dose, beam energy, dose heterogeneity, boost to the surgical cavity, and chemotherapy.
A nomogram was developed using the data from the "Boost Versus No Boost" EORTC 22881-
10882 trial to predict the risk of moderate to severe fibrosis in patients receiving whole breast
radiation.[54] Preventative measures included weighing the risks and benefits of a breast boost,
lowering beam energies, and limiting hot spots to <107% of the prescribed dose. In addition,
patients at high risk for fibrosis may also take pentoxifylline with vitamin E for 6 months after
radiation. This regimen has been shown in small randomized trials to reduce the risk of radiation
fibrosis measured by a tissue compliance meter.[55] Unfortunately, once a patient has developed
breast fibrosis, these changes are mostly irreversible. Management of patients with breast fibrosis
consists mainly of symptomatic treatment, including NSAIDs, SNRIs, and anticonvulsants such
as gabapentin.

Lymphedema

Progressive swelling of the upper extremity may occur in patients treated 6 months after
radiation. The patient may notice increasing arm girth, swelling, heaviness, poor wound healing,
and infection. The risk of developing lymphedema depends on the disruption to the regional
lymphatics. The risk factors include the number of lymph nodes removed, body mass index, and
amount of irradiated lymphatics.[56] A nomogram developed by Gross et al in 2019 may help
quantify this risk.[56] Patients undergoing a sentinel node biopsy have a 5.6% risk of developing
lymphedema compared with a 19.9% risk in those undergoing a full axillary dissection.[57] The
AMAROS trial had a 5-year lymphedema rate of 25% in patients receiving an axillary dissection
versus 12% in those receiving regional nodal radiation alone.[58] Patients receiving axillary
dissection and regional nodal RT would be at the highest risk of developing lymphedema.
Evidence for prevention is sparse but includes weight-bearing exercise and maintaining
appropriate body weight. Patients with lymphedema may be managed with fitted compression
garments, arm elevation, and exercise.

Brachial plexopathy

The brachial plexus trunks may be exposed to radiation doses in patients requiring regional nodal
radiation. Symptoms include hand and arm paresthesia, weakness, and pain in the affected arm
and shoulder. Onset is typically 8 to 12 months after treatment. Fortunately, this rare
complication only affects approximately 1% of all patients. The risk may be increased in patients
who have received chemotherapy or doses of radiation exceeding 50 Gy.[59] Primary prevention
consists of limiting radiation doses to <50 Gy. Patients with brachial plexopathy may be
managed with gabapentin and physical therapy.

Rib fracture

Rib fractures are another rare complication of breast radiotherapy, ranging from 0.3% to 1.8% of
patients.[59][60] The median time to onset is approximately 12 months. The risk is associated
with lower energies and higher doses of radiation. Treatment is generally conservative.

Secondary malignancy

Radiotherapy can induce DNA damage in both cancerous as well as normal tissues, which can
lead to the development of radiation-induced malignancies years after treatment. Large meta-
analyses have shown that patients receiving radiotherapy for breast cancer have an increased risk
of non-breast cancers, including sarcomas, lung, and esophageal cancers.[61] However, the
absolute risk of developing a secondary malignancy is low at 1% to 2% at 10 years.[62] Risk
factors include age, gender, radiation field size, and radiation dose.[63]

Medical Oncology
Chemotherapy, hormone therapy, immunotherapy, and targeted therapy are the systemic
therapies used in breast cancer management and are described below.

Cytotoxic Chemotherapy

Cytotoxic chemotherapy is used in the neoadjuvant and adjuvant setting. Chemotherapy is most
effective in high-grade, poorly differentiated tumors that have a high cell turnover rate, such as
triple-negative and HER2-positive tumors. The chemotherapy regimen depends on tumor
characteristics, the patient's ability to tolerate chemotherapy, and the degree of potential benefit.
[64]

Adjuvant chemotherapy is associated with improved overall survival, disease-free survival, and
reduced local recurrence.[65] Cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)
combination was one of the early regimens used in the adjuvant treatment of breast cancer. More
modern regimens use anthracyclines (eg, doxorubicin or epirubicin) and taxanes in regimens
such as TAC (ie, docetaxel, adriamycin, and cyclophosphamide). Adjuvant chemotherapy is
recommended for most patients with triple-negative and HER2-positive tumors that are >T1
stage. Treatment recommendations for HR-positive tumors are more nuanced and are guided by
commercially available genetic analysis kits (eg, Oncotype Dx, Mammaprint).[66]
[67] Neoadjuvant chemotherapy is increasingly used for triple-negative and HER2-positive
tumors, which leads to increased compliance and tumor downstaging and allows assessment of
the tumor's biological response.[68][69]

Targeted Therapy

Anti-HER2 therapy is indicated in 17% of breast cancers that overproduce the growth-
 promoting protein HER2/neu. Trastuzumab, the first approved drug, is a monoclonal
antibody directly targeting the HER2 protein. It reduces the risk of recurrence and death by
52% and 33%, respectively, if combined with chemotherapy in HER2-positive early breast
cancer if compared to chemotherapy alone.[70][71] More recent data advocates for dual
HER2 blockade with trastuzumab and pertuzumab, which improves response rates.

PARP inhibitors (eg, olaparib and talazoparib) are monoclonal antibodies that prevent the
activation of PARP, which are DNA repair enzymes. They are indicated in the adjuvant
setting in individuals with BRCA mutations and HER2-negative breast cancer.[72]

CDK4/6 inhibitors (palbociclib, target the CDK4/6 proteins, which promote cell division.
Inhibition of this pathway promotes tumor lytic activity in HR-positive HER2-negative
tumors. They are indicated in metastatic HR-positive, HER2-negative tumors and selected
patients with early HR-positive tumors.[73]

Immune checkpoint inhibitors (pembrolizumab, nivolumab) act on the PD-1, PD-L1

pathway to activate the host immune system. They are currently indicated in triple-
negative breast cancer and the metastatic setting.[74]

Hormonal Treatment

Selective estrogen receptor modulators (eg, tamoxifen) or aromatase inhibitors (eg, exemestane
and letrozole) are indicated in HR-positive breast cancers. Estrogen receptor modulators are
especially indicated in premenopausal women, while both drugs can be used postmenopausal.
Hormonal therapy reduces the risk of breast cancer recurrence and mortality and is indicated
from 5 to 10 years.[69][31] Premenopausal women may also benefit from oophorectomy or
chemical suppression of the ovaries (eg, GnRH antagonists), which are the primary source of
estrogen before menopause.[75]

Staging
Breast cancer staging is determined clinically and histologically. Clinical breast cancer staging is
based on physical examination and imaging studies before treatment. Histopathologic breast
cancer staging is determined by pathologic examination of the primary tumor and regional lymph
nodes after definitive surgical treatment. Staging is performed to group patients into risk
categories that define prognosis and guide treatment recommendations for patients with a similar
prognosis. Breast cancer is classified with the TNM classification system, which groups patients
into 4 stage categories based on the primary tumor size (T), the regional lymph nodes status (N),
and if there is any distant metastasis (M).[30] The most widely used TNM system is that of the
American Joint Committee on Cancer.

Primary Tumor (T)

Tis: Carcinoma in-situ, Paget Disease With no Tumor

T1: <2 cmT1a: 0.1 to 0.5 cmT1b: 0.5 to 1.0 cmT1c: 1.0 to 2.0 cm

T2: 2 to 5 cm

T3: >5 cm

T4T4a: Chest wall involvementT4b: Skin involvementT4c: Both 4a and 4bT4d:

Inflammatory ca

Regional Lymph Nodes (N)

N1: Mobile ipsilateral axillary nodes

 N2: Fixed/matted ipsilateral axillary nodes

N3N3a: Ipsilateral infraclavicular nodesN3b: Ipsilateral mammary nodesN3c:

Ipsilateral supraclavicular nodes

Distant Metastases (M)

M1: Distant metastases

Breast Cancer Staging

Stage 0 comprises ductal carcinoma in situ (DCIS) and noninvasive breast cancer. Early invasive
cancer includes stages I, IIa, and IIb. Stages IIIa, IIIb, and IIIc primarily involve locally
advanced disease. Stage IV is all metastatic breast cancer.[68] (see Image. Breast Cancer
Metastasis Sites)

Prognosis
The prognosis of breast cancer depends on the stage. Stage 0 and Stage I both have a 100% 5-
year survival rate. The 5-year survival rate of Stage II and Stage III breast cancer is about 93%
and 72%, respectively. When the disease spreads systemically, its prognosis worsens
dramatically. Only 22% of Stage IV breast cancer patients will survive their next 5 years.[30]

Complications
Complications can arise from the treatment, whether chemotherapy, radiation, hormonal therapy,
or surgery.

Surgical

Infection

Pain

Bleeding

Cosmetic issues

Permanent scarring

Alteration or loss of sensation in the chest area and reconstructed breasts

Chemotherapy

Nausea/vomiting and diarrhea

Hair loss

Memory loss "chemo brain"

Vaginal dryness

Menopausal symptoms/fertility issues

Neuropathy

Hormonal Therapy

Hot flashes

Vaginal discharge dryness

 Fatigue

Nausea

Impotence in males with breast cancer

Radiation

Pain and skin changes

Fatigue

Nausea

Hair loss

Chronic heart and lung issues

Neuropathyy [76][30]

Deterrence and Patient Education

Breast cancer is the most commonly diagnosed cancer in women. Addressing the environmental
and personal factors that increase the risk of breast cancer is vital in reducing breast cancer
incidence. Screening helps detect premalignant lesions and breast cancer before it is clinically
evident. Early detection leads to improved survival. Identifying patients at high risk for breast
cancer is also crucial, as these individuals need to be monitored closely. Mammography,
ultrasound, and MRI may be used for screening and diagnosis. A biopsy with histopathology and
molecular markers should be performed on all patients. Early breast cancer is typically treated
with breast conservation surgery, radiation, chemotherapy, or hormonal therapy. More advanced
tumors require a mix of different modalities to obtain the best outcome. Long-term surveillance
and compliance with therapy help improve survival.

Enhancing Healthcare Team Outcomes

Patient-centered care for individuals with breast requires collaboration among healthcare
professionals, including physicians, advanced practice clinicians, nurses, pharmacists, and others.
These neoplasms are often discovered during screening. The necessary skills involve interpreting
radiological findings, identifying potential complications, effectively communicating these
findings to the patient and their care team, and understanding the intricacies of breasts. Medical
oncology, interventional radiology, pathology, general surgery, plastic surgery, and primary care
practitioners typically play a role in coordinating and delivering care to patients with breast
cancer. The entire healthcare team also plays a crucial role in ensuring that patients continue on
surveillance pathways.

Review Questions

Access free multiple choice questions on this topic.

Click here for a simplified version.

Comment on this article.

Figure

Common Sites of Breast Cancer Metastasis. Medical Gallery of Mikael

Häggström, Public Domain, via Wikimedia Commons
Figure

Breast Mammogram. A mammographic view of the left

breast demonstrates skin thickening, diffusely increased
breast density, and malignant-type calcifications in this
patient with biopsy-proven inflammatory breast cancer.
Contributed by H Barazi, (more...)

Figure

Breast Cancer Risk Factors 5. Kerlikowske K, Gard CC, Tice

JA, et al. for the Breast Cancer Surveillance Consortium.
Risk factors that increase risk of estrogen receptor-positive
and -negative breast cancer. J Natl Cancer Inst. 109(5):
djw276, 2016.

Figure

Breast Estrogen Receptor Staining Contributed by Fabiola

Farci, MD

Figure

Breast Cancer Axillary Lymphadenopathy Contributed by

Sunil Munakomi, MD

Figure

Breast Cancer Fine Needle Aspiration Cytology Contributed

by Sunil Munakomi, MD

Figure

Clinical Signs of Breast Carcinoma Contributed by Sunil

Munakomi, MD

Figure

Pleomorphic Lobular Breast Carcinoma Contributed by

Emma Gregory

Figure
 Invasive Ductal Carcinoma. Histological slide of high-grade ductal carcinoma
in situ with invasive ductal carcinoma (×10). The left side of the image shows a
sheet of cells with pleomorphic nuclei, arranged in tubules, infiltrating into
(more...)

References
1. Watkins EJ. Overview of breast cancer. JAAPA. 2019 Oct;32(10):13-17. [PubMed:
31513033]
2. Alex A, Bhandary E, McGuire KP. Anatomy and Physiology of the Breast during Pregnancy
and Lactation. Adv Exp Med Biol. 2020;1252:3-7. [PubMed: 32816256]
3. Kashyap D, Pal D, Sharma R, Garg VK, Goel N, Koundal D, Zaguia A, Koundal S, Belay A.
Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures. Biomed
Res Int. 2022;2022:9605439. [PMC free article: PMC9038417] [PubMed: 35480139]
4. PDQ Screening and Prevention Editorial Board. PDQ Cancer Information Summaries
[Internet]. National Cancer Institute (US); Bethesda (MD): Apr 10, 2025. Breast Cancer
Screening (PDQ®): Health Professional Version. [PubMed: 26389344]
5. Doren A, Vecchiola A, Aguirre B, Villaseca P. Gynecological-endocrinological aspects in
women carriers of BRCA1/2 gene mutations. Climacteric. 2018 Dec;21(6):529-535.
[PubMed: 30295091]
6. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global
Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36
Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. [PubMed: 33538338]
7. Parada H, Sun X, Tse CK, Olshan AF, Troester MA. Lifestyle Patterns and Survival
Following Breast Cancer in the Carolina Breast Cancer Study. Epidemiology. 2019
Jan;30(1):83-92. [PMC free article: PMC7451223] [PubMed: 30299404]
8. White AJ, Bradshaw PT, Hamra GB. Air pollution and Breast Cancer: A Review. Curr
Epidemiol Rep. 2018 Jun;5(2):92-100. [PMC free article: PMC6159940] [PubMed:
30271702]
9. Gucalp A, Traina TA, Eisner JR, Parker JS, Selitsky SR, Park BH, Elias AD, Baskin-Bey ES,
Cardoso F. Male breast cancer: a disease distinct from female breast cancer. Breast Cancer
Res Treat. 2019 Jan;173(1):37-48. [PMC free article: PMC7513797] [PubMed: 30267249]
10. Azamjah N, Soltan-Zadeh Y, Zayeri F. Global Trend of Breast Cancer Mortality Rate: A 25-
Year Study. Asian Pac J Cancer Prev. 2019 Jul 01;20(7):2015-2020. [PMC free article:
PMC6745227] [PubMed: 31350959]
11. Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer:
collaborative reanalysis of individual data from 52 epidemiological studies including 58,209
women with breast cancer and 101,986 women without the disease. Lancet. 2001 Oct
27;358(9291):1389-99. [PubMed: 11705483]
12. Roulot A, Héquet D, Guinebretière JM, Vincent-Salomon A, Lerebours F, Dubot C, Rouzier
R. Tumoral heterogeneity of breast cancer. Ann Biol Clin (Paris). 2016 Dec 01;74(6):653-
660. [PubMed: 27848916]
13. Prat A, Pineda E, Adamo B, Galván P, Fernández A, Gaba L, Díez M, Viladot M, Arance A,
Muñoz M. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast.
2015 Nov;24 Suppl 2:S26-35. [PubMed: 26253814]
14. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT,
Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE,
Børresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours.
Nature. 2000 Aug 17;406(6797):747-52. [PubMed: 10963602]
15. McCart Reed AE, Kalinowski L, Simpson PT, Lakhani SR. Invasive lobular carcinoma of
the breast: the increasing importance of this special subtype. Breast Cancer Res. 2021 Jan
07;23(1):6. [PMC free article: PMC7792208] [PubMed: 33413533]
16. Roux P, Knight S, Cohen M, Classe JM, Mazouni C, Chauvet MP, Reyal F, Colombo PE,
 Jouve E, Chopin N, Daraï E, Coutant C, Lambaudie E, Houvenaeghel G. Tubular and
mucinous breast cancer: results of a cohort of 917 patients. Tumori. 2019 Feb;105(1):55-62.
[PubMed: 30900967]
17. Cserni G. Histological type and typing of breast carcinomas and the WHO classification
changes over time. Pathologica. 2020 Mar;112(1):25-41. [PMC free article: PMC8138497]
[PubMed: 32202537]
18. Practice Bulletin Number 179: Breast Cancer Risk Assessment and Screening in Average-
Risk Women. Obstet Gynecol. 2017 Jul;130(1):e1-e16. [PubMed: 28644335]
19. Baines CJ. Physical examination of the breasts in screening for breast cancer. J Gerontol.
1992 Nov;47 Spec No:63-7. [PubMed: 1430885]
20. Menta A, Fouad TM, Lucci A, Le-Petross H, Stauder MC, Woodward WA, Ueno NT, Lim
B. Inflammatory Breast Cancer: What to Know About This Unique, Aggressive Breast
Cancer. Surg Clin North Am. 2018 Aug;98(4):787-800. [PubMed: 30005774]
21. Henderson JA, Duffee D, Ferguson T. StatPearls [Internet]. StatPearls Publishing; Treasure
Island (FL): Jan 16, 2023. Breast Examination Techniques. [PubMed: 29083747]
22. Jackson VP. Diagnostic mammography. Radiol Clin North Am. 2004 Sep;42(5):853-70, vi.
[PubMed: 15337421]
23. Mann RM, Kuhl CK, Moy L. Contrast-enhanced MRI for breast cancer screening. J Magn
Reson Imaging. 2019 Aug;50(2):377-390. [PMC free article: PMC6767440] [PubMed:
30659696]
24. Nielsen S, Narayan AK. Breast Cancer Screening Modalities, Recommendations, and Novel
Imaging Techniques. Surg Clin North Am. 2023 Feb;103(1):63-82. [PubMed: 36410354]
25. Magny SJ, Shikhman R, Keppke AL. StatPearls [Internet]. StatPearls Publishing; Treasure
Island (FL): Aug 28, 2023. Breast Imaging Reporting and Data System. [PubMed:
29083600]
26. Radovic N, Ivanac G, Divjak E, Biondic I, Bulum A, Brkljacic B. Evaluation of Breast
Cancer Morphology Using Diffusion-Weighted and Dynamic Contrast-Enhanced MRI:
Intermethod and Interobserver Agreement. J Magn Reson Imaging. 2019 May;49(5):1381-
1390. [PubMed: 30325549]
27. Pediconi F, Marzocca F, Cavallo Marincola B, Napoli A. MRI-guided treatment in the
breast. J Magn Reson Imaging. 2018 Dec;48(6):1479-1488. [PubMed: 30318672]
28. Watanabe Y, Anan K. The decision to perform or omit sentinel lymph node biopsy during
mastectomy for ductal carcinoma in situ should be tailored in accordance with preoperative
findings. Breast Cancer. 2019 Mar;26(2):261-262. [PubMed: 30328007]
29. Verma P, Sharma R, Sharma N, Gulati A, Parashar A, Kaundal A. Fine-Needle Aspiration
Cytology versus Core-Needle Biopsy for Breast Lesions: A Dilemma of Superiority
between the Two. Acta Cytol. 2021;65(5):411-416. [PubMed: 34192704]
30. Gradishar WJ, Moran MS, Abraham J, Aft R, Agnese D, Allison KH, Anderson B, Burstein
HJ, Chew H, Dang C, Elias AD, Giordano SH, Goetz MP, Goldstein LJ, Hurvitz SA,
Isakoff SJ, Jankowitz RC, Javid SH, Krishnamurthy J, Leitch M, Lyons J, Mortimer J, Patel
SA, Pierce LJ, Rosenberger LH, Rugo HS, Sitapati A, Smith KL, Smith ML, Soliman H,
Stringer-Reasor EM, Telli ML, Ward JH, Wisinski KB, Young JS, Burns J, Kumar R. Breast
Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr
Canc Netw. 2022 Jun;20(6):691-722. [PubMed: 35714673]
31. Kerr AJ, Dodwell D, McGale P, Holt F, Duane F, Mannu G, Darby SC, Taylor CW.
Adjuvant and neoadjuvant breast cancer treatments: A systematic review of their effects on
mortality. Cancer Treat Rev. 2022 Apr;105:102375. [PMC free article: PMC9096622]
[PubMed: 35367784]
32. Shien T, Iwata H. Adjuvant and neoadjuvant therapy for breast cancer. Jpn J Clin Oncol.
2020 Mar 09;50(3):225-229. [PubMed: 32147701]
33. Waks AG, Winer EP. Breast Cancer Treatment: A Review. JAMA. 2019 Jan 22;321(3):288-
300. [PubMed: 30667505]
34. Czajka ML, Pfeifer C. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL):
 Feb 8, 2023. Breast Cancer Surgery. [PubMed: 31971717]
35. Goethals A, Menon G, Rose J. StatPearls [Internet]. StatPearls Publishing; Treasure Island
(FL): Nov 10, 2024. Mastectomy. [PubMed: 30855800]
36. Sevensma KE, Lewis CR. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL):
Jul 3, 2023. Axillary Sentinel Lymph Node Biopsy. [PubMed: 31985977]
37. Menon G, Lewis CR. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jan
21, 2025. Axillary Lymphadenectomy. [PubMed: 32491796]
38. Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, Land SR,
Margolese RG, Swain SM, Costantino JP, Wolmark N. Long-term outcomes of invasive
ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24
randomized clinical trials for DCIS. J Natl Cancer Inst. 2011 Mar 16;103(6):478-88. [PMC
free article: PMC3107729] [PubMed: 21398619]
39. Litière S, Werutsky G, Fentiman IS, Rutgers E, Christiaens MR, Van Limbergen E, Baaijens
MH, Bogaerts J, Bartelink H. Breast conserving therapy versus mastectomy for stage I-II
breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial. Lancet
Oncol. 2012 Apr;13(4):412-9. [PubMed: 22373563]
40. Wang X, Xu L, Yin Z, Wang D, Wang Q, Xu K, Zhao J, Zhao L, Yuan Z, Wang P.
Locoregional recurrence-associated factors and risk-adapted postmastectomy radiotherapy
for breast cancer staged in cT1-2N0-1 after neoadjuvant chemotherapy. Cancer Manag Res.
2018;10:4105-4112. [PMC free article: PMC6174313] [PubMed: 30323666]
41. Tang L, Matsushita H, Jingu K. Controversial issues in radiotherapy after breast-conserving
surgery for early breast cancer in older patients: a systematic review. J Radiat Res. 2018
Nov 01;59(6):789-793. [PMC free article: PMC6251423] [PubMed: 30321392]
42. Kirby AM. Updated ASTRO guidelines on accelerated partial breast irradiation (APBI): to
whom can we offer APBI outside a clinical trial? Br J Radiol. 2018
May;91(1085):20170565. [PMC free article: PMC6190767] [PubMed: 29513031]
43. Vicini FA, Cecchini RS, White JR, Arthur DW, Julian TB, Rabinovitch RA, Kuske RR,
Ganz PA, Parda DS, Scheier MF, Winter KA, Paik S, Kuerer HM, Vallow LA, Pierce LJ,
Mamounas EP, McCormick B, Costantino JP, Bear HD, Germain I, Gustafson G, Grossheim
L, Petersen IA, Hudes RS, Curran WJ, Bryant JL, Wolmark N. Long-term primary results of
accelerated partial breast irradiation after breast-conserving surgery for early-stage breast
cancer: a randomised, phase 3, equivalence trial. Lancet. 2019 Dec 14;394(10215):2155-
2164. [PMC free article: PMC7199428] [PubMed: 31813636]
44. Bartelink H, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A,
Jager JJ, Hoogenraad WJ, Oei SB, Wárlám-Rodenhuis CC, Pierart M, Collette L. Impact of
a higher radiation dose on local control and survival in breast-conserving therapy of early
breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-
10882 trial. J Clin Oncol. 2007 Aug 01;25(22):3259-65. [PubMed: 17577015]
45. Overgaard M, Nielsen HM, Tramm T, Højris I, Grantzau TL, Alsner J, Offersen BV,
Overgaard J., DBCG Radiotherapy Group. Postmastectomy radiotherapy in high-risk breast
cancer patients given adjuvant systemic therapy. A 30-year long-term report from the
Danish breast cancer cooperative group DBCG 82bc trial. Radiother Oncol. 2022
May;170:4-13. [PubMed: 35288227]
46. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE,
Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC,
Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T,
Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl
DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Radiotherapy or surgery of the axilla
after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a
randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014
Nov;15(12):1303-10. [PMC free article: PMC4291166] [PubMed: 25439688]
47. Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, Vallis KA, White
JR, Rousseau P, Fortin A, Pierce LJ, Manchul L, Chafe S, Nolan MC, Craighead P, Bowen
 J, McCready DR, Pritchard KI, Gelmon K, Murray Y, Chapman JA, Chen BE, Levine MN.,
MA.20 Study Investigators. Regional Nodal Irradiation in Early-Stage Breast Cancer. N
Engl J Med. 2015 Jul 23;373(4):307-16. [PMC free article: PMC4556358] [PubMed:
26200977]
48. Choi KH, Ahn SJ, Jeong JU, Yu M, Kim JH, Jeong BK, Lee JH, Kim SH, Lee JH.
Postoperative radiotherapy with intensity-modulated radiation therapy versus 3-dimensional
conformal radiotherapy in early breast cancer: A randomized clinical trial of KROG 15-03.
Radiother Oncol. 2021 Jan;154:179-186. [PubMed: 32980384]
49. Pignol JP, Truong P, Rakovitch E, Sattler MG, Whelan TJ, Olivotto IA. Ten years results of
the Canadian breast intensity modulated radiation therapy (IMRT) randomized controlled
trial. Radiother Oncol. 2016 Dec;121(3):414-419. [PubMed: 27637858]
50. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, Correa C,
Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall
P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J
Med. 2013 Mar 14;368(11):987-98. [PubMed: 23484825]
51. Epler GR, Kelly EM. Systematic review of postradiotherapy bronchiolitis obliterans
organizing pneumonia in women with breast cancer. Oncologist. 2014 Dec;19(12):1216-26.
[PMC free article: PMC4257753] [PubMed: 25361622]
52. Taghian AG, Assaad SI, Niemierko A, Floyd SR, Powell SN. Is a reduction in radiation
lung volume and dose necessary with paclitaxel chemotherapy for node-positive breast
cancer? Int J Radiat Oncol Biol Phys. 2005 Jun 01;62(2):386-91. [PubMed: 15890579]
53. Williams NR, Williams S, Kanapathy M, Naderi N, Vavourakis V, Mosahebi A. Radiation-
induced fibrosis in breast cancer: A protocol for an observational cross-sectional pilot study
for personalised risk estimation and objective assessment. Int J Surg Protoc. 2019;14:9-13.
[PMC free article: PMC6913559] [PubMed: 31851743]
54. Collette S, Collette L, Budiharto T, Horiot JC, Poortmans PM, Struikmans H, Van den
Bogaert W, Fourquet A, Jager JJ, Hoogenraad W, Mueller RP, Kurtz J, Morgan DA, Dubois
JB, Salamon E, Mirimanoff R, Bolla M, Van der Hulst M, Wárlám-Rodenhuis CC,
Bartelink H., EORTC Radiation Oncology Group. Predictors of the risk of fibrosis at 10
years after breast conserving therapy for early breast cancer: a study based on the EORTC
Trial 22881-10882 'boost versus no boost'. Eur J Cancer. 2008 Nov;44(17):2587-99.
[PubMed: 18757193]
55. Jacobson G, Bhatia S, Smith BJ, Button AM, Bodeker K, Buatti J. Randomized trial of
pentoxifylline and vitamin E vs standard follow-up after breast irradiation to prevent breast
fibrosis, evaluated by tissue compliance meter. Int J Radiat Oncol Biol Phys. 2013 Mar
01;85(3):604-8. [PubMed: 22846413]
56. Gross JP, Whelan TJ, Parulekar WR, Chen BE, Rademaker AW, Helenowski IB, Donnelly
ED, Strauss JB. Development and Validation of a Nomogram to Predict Lymphedema After
Axillary Surgery and Radiation Therapy in Women With Breast Cancer From the NCIC
CTG MA.20 Randomized Trial. Int J Radiat Oncol Biol Phys. 2019 Sep 01;105(1):165-173.
[PubMed: 31085285]
57. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after
breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013 May;14(6):500-
15. [PubMed: 23540561]
58. Bartels SAL, Donker M, Poncet C, Sauvé N, Straver ME, van de Velde CJH, Mansel RE,
Blanken C, Orzalesi L, Klinkenbijl JHG, van der Mijle HCJ, Nieuwenhuijzen GAP,
Veltkamp SC, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JWS,
Belkacemi Y, Petignat P, Schinagl DAX, Coens C, van Tienhoven G, van Duijnhoven F,
Rutgers EJT. Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast
Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS
Trial. J Clin Oncol. 2023 Apr 20;41(12):2159-2165. [PubMed: 36383926]
59. Pierce SM, Recht A, Lingos TI, Abner A, Vicini F, Silver B, Herzog A, Harris JR. Long-
term radiation complications following conservative surgery (CS) and radiation therapy
 (RT) in patients with early stage breast cancer. Int J Radiat Oncol Biol Phys.
1992;23(5):915-23. [PubMed: 1639653]
60. Meric F, Buchholz TA, Mirza NQ, Vlastos G, Ames FC, Ross MI, Pollock RE, Singletary
SE, Feig BW, Kuerer HM, Newman LA, Perkins GH, Strom EA, McNeese MD, Hortobagyi
GN, Hunt KK. Long-term complications associated with breast-conservation surgery and
radiotherapy. Ann Surg Oncol. 2002 Jul;9(6):543-9. [PubMed: 12095969]
61. Grantzau T, Overgaard J. Risk of second non-breast cancer after radiotherapy for breast
cancer: a systematic review and meta-analysis of 762,468 patients. Radiother Oncol. 2015
Jan;114(1):56-65. [PubMed: 25454172]
62. Ye JC, Yan W, Christos P, Nori D, Chao KS, Ravi A. Second cancer, breast cancer, and
cardiac mortality in stage T1aN0 breast cancer patients with or without external beam
radiation therapy: a national registry study. Clin Breast Cancer. 2015 Feb;15(1):54-9.
[PubMed: 25223278]
63. Dracham CB, Shankar A, Madan R. Radiation induced secondary malignancies: a review
article. Radiat Oncol J. 2018 Jun;36(2):85-94. [PMC free article: PMC6074073] [PubMed:
29983028]
64. Burguin A, Diorio C, Durocher F. Breast Cancer Treatments: Updates and New Challenges.
J Pers Med. 2021 Aug 19;11(8) [PMC free article: PMC8399130] [PubMed: 34442452]
65. Amjad MT, Chidharla A, Kasi A. StatPearls [Internet]. StatPearls Publishing; Treasure
Island (FL): Feb 27, 2023. Cancer Chemotherapy. [PubMed: 33232037]
66. Syed YY. Oncotype DX Breast Recurrence Score®: A Review of its Use in Early-Stage
Breast Cancer. Mol Diagn Ther. 2020 Oct;24(5):621-632. [PubMed: 32613290]
67. Andre F, Ismaila N, Allison KH, Barlow WE, Collyar DE, Damodaran S, Henry NL,
Jhaveri K, Kalinsky K, Kuderer NM, Litvak A, Mayer EL, Pusztai L, Raab R, Wolff AC,
Stearns V. Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast
Cancer: ASCO Guideline Update. J Clin Oncol. 2022 Jun 01;40(16):1816-1837. [PubMed:
35439025]
68. Trayes KP, Cokenakes SEH. Breast Cancer Treatment. Am Fam Physician. 2021 Aug
01;104(2):171-178. [PubMed: 34383430]
69. Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, Khan SA, Loibl
S, Morris EA, Perez A, Regan MM, Spears PA, Sudheendra PK, Symmans WF, Yung RL,
Harvey BE, Hershman DL. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted
Therapy for Breast Cancer: ASCO Guideline. J Clin Oncol. 2021 May 01;39(13):1485-
1505. [PMC free article: PMC8274745] [PubMed: 33507815]
70. Wu YT, Xu Z, Zhang K, Wu JS, Li X, Arshad B, Li YC, Wang ZL, Li HY, Wu KN, Kong
LQ. Efficacy and cardiac safety of the concurrent use of trastuzumab and anthracycline-
based neoadjuvant chemotherapy for HER2-positive breast cancer: a systematic review and
meta-analysis. Ther Clin Risk Manag. 2018;14:1789-1797. [PMC free article:
PMC6165855] [PubMed: 30310287]
71. Dieci MV, Vernaci G, Guarneri V. Escalation and de-escalation in HER2 positive early
breast cancer. Curr Opin Oncol. 2019 Jan;31(1):35-42. [PubMed: 30325338]
72. Ye F, Dewanjee S, Li Y, Jha NK, Chen ZS, Kumar A, Vishakha, Behl T, Jha SK, Tang H.
Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer.
Mol Cancer. 2023 Jul 06;22(1):105. [PMC free article: PMC10324146] [PubMed:
37415164]
73. Husinka L, Koerner PH, Miller RT, Trombatt W. Review of cyclin-dependent kinase 4/6
inhibitors in the treatment of advanced or metastatic breast cancer. J Drug Assess. 2020 Dec
18;10(1):27-34. [PMC free article: PMC7751387] [PubMed: 33414982]
74. Debien V, De Caluwé A, Wang X, Piccart-Gebhart M, Tuohy VK, Romano E, Buisseret L.
Immunothérapie dans le cancer du sein : un aperçu des stratégies et perspectives actuelles.
Cancer du sein NPJ. 13 février 2023 ; 9 (1):7. [ Article gratuit PMC: PMC9925769 ] [
PubMed: 36781869 ]
75. Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G. Cancer du sein. Lancet. 8 mai
 2021 ; 397 (10286) : 1750-1769. [ PubMed: 33812473 ]
76. Al-Hilli Z, Wilkerson A. Chirurgie du sein : prise en charge des complications
postopératoires après une intervention pour cancer du sein. Surg Clin North Am. 2021 oct. ;
101 (5) : 845-863. [ PubMed: 34537147 ]
77. Pike M. Formation des commis d'unité. Hôpitaux. 16 mai 1970 ; 44 (10) : 94 passim. [
PubMed: 5444545 ]

Déclaration : Gopal Menon déclare n'avoir aucune relation financière pertinente avec des sociétés non
admissibles.

Déclaration : Fadi Alkabban déclare n'avoir aucune relation financière pertinente avec des sociétés non
admissibles.

Déclaration : Troy Ferguson déclare n'avoir aucune relation financière pertinente avec des entreprises non
admissibles.

Droits d'auteur © 2026, StatPearls Publishing LLC.

Cet ouvrage est diffusé selon les termes de la licence Creative Commons Attribution - Pas d’Utilisation Commerciale - Pas de
Modification 4.0 International (CC BY-NC-ND 4.0) ( [Link] ), qui autorise la
diffusion de l’œuvre, à condition que l’article ne soit ni modifié ni utilisé à des fins commerciales. Vous n’avez pas besoin
d’obtenir d’autorisation pour diffuser cet article, à condition de mentionner l’auteur et la revue.

Identifiant de l'étagère : NBK482286 PMID : 29493913