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312
S. C. Wimann et al.
Breast cancer in pregnancy
Adjuvant therapy Antihormonal therapy is contraindicated during pregnancy or breastfeeding
Radiation therapy is contraindicated during pregnancy
Chemotherapy is safe during second and third trimesters of pregnancy (except for folate
scavenging drugs like methotrexate)
Breast Cancer inMales
Breast cancer in males
0.5–1% of all breast cancer
No difference between staging and outcomes for men and women (men present at a later
Characteristics
Risk factors Conditions associated with an abnormal estrogen-to-androgen ratio (cirrhosis,
Diagnosis
stage)
Genetic testing is recommended in all male patients with breast cancer
Most common is invasive ductal carcinoma, ER/PR+ and HER2 negative
Klinefelter syndrome, obesity, and nasteride), radiation exposure
Distinguish between gynecomastia, pseudogynecomastia, and breast cancer on physical
exam
Gynecomastia Mostly concentric and primarily subareolar with a rubbery
consistency; bilateral symmetrical and retroareolar
Pseudogynecomastia Consists mainly of fatty tissue, without broglandular tissue
Management
Follow-up
Male breast cancer Hard, irregular, nontender, eccentric mass often xed to the
chest wall
Diagnosis and staging same as female breast cancer
DCIS ➔ mastectomy
Breast conservative therapy+radiation
Simple mastectomy+SLNB
Endocrine therapy and chemotherapy ➔ same as female breast cancer
Adjuvant tamoxifen rather than aromatase inhibitors is recommended
T4 cancers and/or LN metastasis ➔ neoadjuvant chemotherapy
Physical examination every 3–4 months for the rst 2years➔ then twice annually for
5years ➔ then annually
10 Breast andOncology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Hereditary Breast Cancer
Mutation Associated cancers Breast pathology
313
BRAC 1 Female breast cancer (60% lifetime risk)
Ovarian cancer (40% lifetime risk)
BRAC 2 • Female breast cancer (60% lifetime risk)
• Ovarian cancer (10% lifetime risk)
• Male breast cancer (10% lifetime risk)
• Prostate, pancreatic cancers, and melanoma
P53 (Li-Fraumeni
syndrome)
PTEN (Cowden
syndrome)
PALB2 Breast and pancreatic cancers
CDH1 Breast and gastric cancer
Breast, brain, lung, and hematologic
malignancies (leukemia), sarcoma; and adrenal
cortical carcinoma
Breast, thyroid, and genitourinary tract cancers,
mucocutaneous lesions, GI hamartomas
• Higher tumor grade and cell
proliferation
• Less in situ carcinoma associated
with invasive cancer
• Higher occurrence of medullary
carcinoma
• Lower frequency of hormone
receptor–positive tumors (more
commonly triple negative) and
basal phenotype
ER+ and HER2-negative (luminal B
subtype)
• Lower tumor grade and cell
proliferation
• Higher occurrence of
tubulolobular invasive carcinoma
and invasive cribriform
carcinoma
Bilateral breast cancer
Breast cancer is seen in 25–50% by
age 50
ATM (ataxia
telangiectasia)
CHEK2 Breast, colorectal, and bladder cancers
Breast cancer, cerebellar and neuromotor
deterioration, lymphoma and leukemia
Treatment options for patient with familial breast cancer
Treatment options Recommended for Risk reduction
Bilateral prophylactic
mastectomy
Prophylactic oophorectomy Carriers of BRCA mutations Reduce risk of breast cancer by ~50% in
Chemoprevention (selective
estrogen receptor modulators)
Carriers of BRCA mutations Reduces risk of breast cancer by ~95%
premenopausal women
Reduces ovarian and fallopian tube cancer
risk
Carriers of a BRCA mutation who
has been previously diagnosed
with breast cancer
Reduces contralateral breast cancer risk in
women with BRCA1 and BRCA2 mutations
314
S. C. Wimann et al.
Screening recommendations for patients with BRCA mutations
Annual MRI starting at age 25
Annual mammogram starting at age 30
Annual ovarian cancer screening (transvaginal ovarian ultrasounds, cancer antigen-125, pelvic examinations)
starting at age 30
Biannual clinical breast examination beginning at age 25
Monthly self-breast examination starting at age 18
Surgical Options fortheBreast
Breast conservative therapy
• Multicentric disease in separate quadrants
• Diffuse malignant microcalcications
Contraindications
• Prior irradiation of the chest or breast
• Pregnancy
• Persistent positive margins after re-excision
• Large tumor compared to breast size
• Patients who are unable to receive adjuvant
radiation (connective tissue disorders like
scleroderma and active lupus, previous
radiation to the breast)
Multifocal
>5cm
Multicentric
Key steps
Conrm retrieval of the preoperative biopsy clip
in the specimen using radiologic conrmation
Radiologic-pathologic correlation: Pathology
obtained from a biopsy can explain the
radiographic features for which the biopsy was
obtained
Lumpectomy or quadrantectomy
Positive margin found on nal pathology
➔either another margin re-excision or a
mastectomy is required to achieve a negative
margin on nal excision
10 Breast andOncology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Research
Reference Findings
315
Moran MS, Schnitt SJ, Giuliano AE, etal. Society of
Surgical Oncology–American Society for Radiation
Oncology consensus guideline on margins for breastconserving surgery with whole-breast irradiation in
stages I and II invasive breast cancer. J Clin Oncol.
2014;32(14):1507–1515
Positive margins management
Findings of a positive margin on nal pathology is
associated with a twofold increase inlocal recurrence,
regardless of tumor subtype
Breast cancer recurrence
Positive margins are associated with a higher incidence
of breast recurrence rate compared with patients with
negative margins
Addition of radiation boost does not eliminate this
disparity
Postoperative complications after BCT and mastectomy
Complications Characteristics Treatment
Risk factors: inadequate intraoperative
Hematoma
Lymphedema
Wound infection Risk factors include smoking, diabetes,
hemostasis and impaired coagulation
Risk factors: axillary node dissection,
increasing number of axillary nodes
removed, removal of axillary nodes
superior to the axillary vein,
mastectomy, and higher body mass
index
age, and obesity
Compression wrapping
Return to the operating room for wound exploration
and hemostasis
Physical therapy, range-of-motion exercises, and
compression wrapping
Oral or intravenous antibiotics
Abscess ➔ incision and drainage or aspiration
Skin necrosis
Seromas
Chronic
postmastectomy
pain
Risk factors: prior radiation treatment,
obesity, older age, smoking history,
excessive electrocautery, thin skin ap,
tension on closure of the incision, and
tumescence solution with epinephrine
Incidence of 10–18% following
mastectomy
Most seromas are reabsorbed within a
month, but this process can take up to a
year
Pain involves axilla, upper arm, and
chest wall
Incidence up to 10% of postop patients
Phantom breast syndrome may also
persist for years following mastectomy
Topical nitroglycerin, decreasing the size of
expander if in place, removal of an implant if in
place, and debridement of necrotic tissue
Full-thickness necrosis ➔ surgical debridement or
skin grafting
Seromas following lumpectomy ➔ are transient ➔
do not require further aspiration or drainage
If seromas show signs of infection ➔ it should be
opened and drained percutaneously + antibiotics
If seromas are symptomatic (excessively large, or
are placing tension on the incision) ➔ aspiration or
drainage
316
S. C. Wimann et al.
Sentinel Lymph Node Biopsy andAxillary Lymph Node Dissection
Sentinel lymph node biopsy
Indications for SLNB Contraindications
Indications and contraindications
Key surgical steps
• No clinically positive axillary
nodes
• T1-T2 breast cancer
• Patients with DCIS
undergoing mastectomy
• Lymph nodes that are clinically
positive
• Inammatory breast cancer (T4d)
• Locally advanced breast cancer
• Recent major reduction
mammoplasty or axillary surgery
Types of SLNB Key things to know
Radioisotope (technetium
Can be used in pregnancy
sulfur)
1% isosulfan blue dye Can cause severe anaphylactic reaction
Avoid in pregnancy
Methylene blue • Can cause skin necrosis and pain
• Can cause pulmonary edema and
serotonin syndrome in patients
taking serotonergic medications
• Can be used in pregnancy
• Sentinel lymph node is usually found in the external mammary group
• Any palpable suspicious node should be removed
• Remove the lymph node with radioactivity as measured by gamma
probe
• All nodes with counts >10% of highest count should be removed
• If activity is <10% of the highest activity lymph node ➔ Biopsy complete
➔If no sentinel node is identied ➔ ALND should be performed
Axillary lymph node
dissection
Axillary vein
➔superiorly
Serratus anterior
muscle➔ medially
Latissimus dorsi
muscle➔ laterally
Axilla is
bordered
by:
Subscapularis and
teres minor muscles
➔posteriorly
Pectoralis major and
minor + subclavius
muscle and
clavipectoral fascia
➔anteriorly
Angular vein ➔
inferiorly
Lateral Border
Intertubecular
sulcus
Coracobrachialis
Anterior Border
Pectoralis major and minor
Biceps
Medial Border
Serratus anterior
and thoracic wall
Posterior Border
Scapularis, teres major,
latissimus, dorsi
10 Breast andOncology
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Axillary lymph node
dissection
317
Key surgical
steps
• Surgery in the axilla is performed without paralysis ➔ to facilitate nerve identication and
monitor function
• Preserve medial pectoral neurovascular bundle
• Identify the long thoracic nerve along the serratus anterior muscle
• Identify the thoracodorsal neurovascular bundle along the latissimus dorsi muscle
• Identify the intercostobrachial nerves ➔ preserve if possible
• Excise all nodes from level I and II
• Leave a negative pressure drain (drain can be removed postoperatively when output is <30 ml/24
hours)
Research
References Findings
Takei H, Suemasu K,
Kurosumi M, etal. Added
value of the presence of blue
nodes or hot nodes in sentinel
lymph node biopsy of breast
cancer. Breast Cancer.
2006;13(2):179–185
Tvedskov TF, Jensen M-B,
Ejlertsen B, Christiansen P,
Balslev E, Kroman
N.Prognostic signicance of
axillary dissection in breast
cancer patients with
micrometastases or isolated
tumor cells in sentinel nodes: a
nationwide study. Breast
Cancer Res Treat.
2015;153(3):599–606
Sentinel lymph node biopsy using Radiocolloid vs blue dye:
The combination of radiocolloid and blue dye resulted in a signicantly higher
success rate in SLN mapping with a lower false-negative rate as compares with
blue dye alone
Isolated tumor cells and micrometastasis in axillary lymph nodes:
Type of tumor cells
in SLNB
Isolated tumor cells
(ITCs)
Micrometastases Cluster of metastatic
Denition Management
Cluster of metastatic
tumor cells in lymph
nodes measuring <0.2mm
or fewer than 200 cells
tumor cells in lymph
nodes measuring between
0.2–2mm
Likelihood that the remainder
of lymph nodes have tumor is
low
➔no need for ALND
➔no need for chest wall
radiation
➔not an indication for
chemotherapy
Complications associated with SLNB
Complications Description Management
Allergic reaction to
Isosulfan blue
Sensory decits Most common from a nerve that provides
Lymphedema Occur in about 3% of cases Physical therapy
Dye injection with isosulfan blue can
cause an allergic reaction
sensation to the chest wall
Manage allergic reaction
Supportive measure ➔resolves within
3months
Compression garments
Manual lymphatic drainage performed by
physical therapists
318
S. C. Wimann et al.
Complications associated with ALND
Complications Description Treatment
Lymphedema Incidence range from 20–50%
Incidence higher in patients who also received
radiation therapy
Motor nerve injury Motor nerves are at greater risk for injury during
ALND than during SLNB
Sensory nerve
decit
Sensory decits to the skin are more common
with ALND than SLNB
Caused by injury to intercostal brachial
nerves➔causes sensory loss of the proximal
medial arm
Reconstruction After Mastectomy
Reconstruction options and complications
Types Ideal candidate
• Latissimus dorsi
myocutaneous
• Ample tissue at the desired
donor site
Physical therapy to improve the range of
motion
Compression garments can reduce
swelling
Manual lymphatic drainage performed
by physical therapists
Physical therapy
Some of the decits will resolve, but
often there is some permanent sensory
loss to the skin overlying the axilla
Postoperative
complications
Most common cause of ap
necrosis is venous thrombosis
Flap-based
breast
reconstruction
Implant- based
reconstruction
• Transverse rectus
abdominus myocutaneous
(TRAM) ap (pedicled or
free ap)
• Deep inferior epigastric
perforator (DIEP) ap
• Supercial inferior
epigastric artery (SIEA)
ap
• Gluteal artery perforator
(GAP) ap
Saline-lled implant or a
silicone-lled implant
• Personal history of
previous radiation to the
breast
• Multiple scars on the
breast
• Bilateral mastectomies
and any of the above
characteristics
• When wide excision ➔
autogenous tissue is
preferred to implants
• BMI <30
• Patients with active
lifestyles who desire a
shorter recovery time
Vascular compromise is most
likely to occur in the rst 24h
postoperatively➔ monitor in an
intensive care unit setting and
hourly vascular checks with
Doppler
Smokers and diabetics ➔are at
increased risk for necrosis of the
skin aps, the abdominal ap,
and for the development of an
abdominal hernia ➔risk can be
managed if the patient stops
smoking for at least 4weeks
before the surgical procedure
• Hematoma
• Seroma
• Implant infection
• Implant malposition
• Mastectomy skin ap
necrosis
• Breast implant-associated
anaplastic large cell
lymphoma (BIA-ALCL)
10 Breast andOncology
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Reconstruction options and complications
Types Ideal candidate
319
Postoperative
complications
Fat grafting
Uses the patient’s own fat that
is liposuctioned from one part
of the patient’s body, puried,
and then injected into the
breast
Fat grafting is safe and does not
increase the risk of future breast
cancer
Does not interfere with future
breast imaging
Breast Implant–associated anaplastic large cell lymphoma (BIA-ALCL):
Incidence 1in 30,000 women with textured implants
Presentation Occurs after 8–10 years of implant placement
Breast enlargement and a uid collection around the implant
Diagnosis Needle aspiration of the peri-implant seroma, with uid cytologic and pathologic evaluation
Management Highly treatable lymphoma
Immediate versus delayed reconstructions
Immediate reconstruction Delayed reconstruction
Indications
Prophylactic mastectomy
Mastectomy for invasive or in situ
carcinoma
*Chemotherapy is not a
contraindication for immediate
reconstruction
• Inammatory breast cancer
• Patients at increased risk for adverse outcomes due to
comorbidities
• When postop radiation is planned because of increased
wound dehiscence
• For women who are likely to need postmastectomy
radiation therapy➔ place an implant or tissue expander
• Implants can become rm (capsular contracture) and
autologous aps can shrink or atrophy
Rationale
• It is preferred to radiate implants because the implant can
be replaced with a ap if necessary
• Autologous reconstruction can be performed 6–12months
later
320
Palpable nodules in postmastectomy breast reconstruction patients
• It is impossible to remove all of the breast tissue with a mastectomy
Causes
Diagnosis
Treatment Same as breast cancer
Patients who have had a mastectomy for cancer can still have local recurrence of their disease
• Possibility of fat necrosis in implant- based or autologous reconstruction
• Imaging followed by biopsy if imaging is indeterminate or suspicious
• Mammography (implant-displacement views to maximize the amount of breast tissue evaluated)
• Fat necrosis often has pathognomonic mammogram ndings (calcications)
• If diagnosis is conrmed ➔no treatment
Oncology
Tumor Immunology
Tumor immunology
Various immune cell types in both the innate immune system and the adaptive immune system are
involved in tumor recognition and defense
Cell Type Function
S. C. Wimann et al.
Cell Types
Involved in
Tumor
Recognition
and Rejection
T cells CD8+ and CD4+ lymphocytes initiate the distinction between self and
non-self
Natural Killer cells Part of the innate immune system
Target cells with low MHC class I expression for destruction
Macrophages Macrophages differentiate into at least two different phenotypes:
M1 macrophages ➔ release IFN-γ ➔ responsible for phagocytosis
M2 macrophages ➔ release cytokines such as IL-4, IL-10, TGF-β ➔
mitigate inammatory responses
Dendritic cells Antigen-presenting cells (APCs) responsible for processing antigens and
presenting them to the immune system
10 Breast andOncology
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Tumor immunology
321
Immune
synapse
The interaction between T cell receptors and MHC proteins of APCs ➔represents the rst step for
the activation of resting T cells
Additional costimulatory signals complete the activation
The T cell receptor (TCR) complex consists of three major components: the TCR itself, the CD4
or CD8 receptor, and the CD3 molecule
The TCR binds specic short stretches of amino acids presented by MHC molecules
MHC class 1 is expressed by all nucleated cells and is recognized by CD8+ T cells
MHC class 2 molecules are expressed by APCs and are recognized by CD4+ T cells
This costimulatory process is tightly regulated by both “agonist” molecules and inhibitory signals
on both the APC and T cells ➔ collectively referred to as “immune checkpoint” molecules
Examples of co-inhibitory or “immune checkpoint” molecules include cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death-1 (PD-1)
Although part of the innate immune system, NK cells can interact with the adoptive immune
system
NK cells along with T cells are involved in multiple cytotoxic pathways
Immunoglobulins are capable of binding to antigens and triggering the immune response➔ as
antibody- dependent cell-mediated cytotoxicity
Immunoglobulins are also involved in the activation of the complement system that eventually
leads to death of targeted cells
There are several mechanisms that tumor cells use for escape from immune surveillance:
Tumors can lose major MHC class 1 expression or the intracellular machinery required to
transport tumor antigens to the tumor surface for T cell recognition ➔ evade the immune response
Tumor evasion
of immune
surveillance
Cancer cells are able to create an immunosuppressive microenvironment ➔ survive and evade the
immune response
Types of immunotherapies
Type Characteristics Indications Side effects
Cytokine
therapy
Initial approaches to
immunotherapy
Use has been largely
supplanted by the use of
checkpoint inhibitors
IFN-α ➔ previously used
adjuvant treatment for node
positive melanoma
IL-2 ➔ previously used
metastatic melanoma
Flulike symptoms and fatigue
(because this adjuvant treatment
is performed over 1year, it is
difcult to tolerate)
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