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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_901_Библиотеки_им_академика_М_И_Перельмана
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302
Research
References Findings
S. C. Wimann et al.
EORTC phase III Trial:
Stupp R, Hegi ME, Mason WP, etal. Effects of
radiotherapy with concomitant and adjuvant
temozolomide versus radiotherapy alone on survival in
glioblastoma in a randomised phase III study: 5-year
analysis of the EORTC-NCIC trial. Lancet Oncol.
2009;10(5):459–466
Marinovich ML, Azizi L, Macaskill P, etal. The
association of surgical margins and local recurrence in
women with ductal carcinoma in situ treated with
breast- conserving therapy: a meta-analysis. Ann Surg
Oncol. 2016;23(12):3811–3821
National Surgical Adjuvant Breast and Bowel Project
(NSABP) P-1 trial:
Fisher B, Costantino JP, Wickerham DL, etal. Tamoxifen
for prevention of breast cancer: report of the National
Surgical Adjuvant Breast and bowel project P-1 study. J
Natl Cancer Inst. 1998;90(18):1371–1388
NSABP Study of Tamoxifen and Raloxifene (STAR or P-2
trial):
Vogel VG, Costantino JP, Wickerham DL, etal. Update of
the National Surgical Adjuvant Breast and bowel project
study of Tamoxifen and raloxifene (STAR) P-2 trial:
Preventing breast cancer. Cancer Prev Res (Phila).
2010;3(6):696–706
International Breast Cancer Intervention Study
(IBIS-II):
Cuzick J, Sestak I, Forbes JF, etal. Use of anastrozole
for breast cancer prevention (IBIS-II): long-term results
of a randomized controlled trial. Lancet.
2020;395(10218):117–122
Radiation therapy after local excision for DCIS
continued to reduce risk of local recurrence (47%
reduction at 10years)
Systematic review of 20 studies ➔ optimal margin
for DCIS: 2mm margin
Tamoxifen conferred a risk reduction (in hormone
receptor–positive cancer) of 59% in women with
LCIS and 86% in women with ADH or lobular
hyperplasia
Raloxifene was found to be equivalent to tamoxifen
in reducing the incidence of invasive breast cancer
(50% reduction) and had fewer side effects
Raloxifene has a better side effect prole but is
inferior to tamoxifen in reducing the risk of DCIS
Anastrozole (an aromatase inhibitor) reduced the
incidence of DCIS and invasive cancer by 50% in
postmenopausal women at an increased risk for
developing breast cancer
Risk reduction therapy
Patient with high-risk lesion requiring risk
reduction therapy:
Premenopausal women Tamoxifen
Postmenopausal women Tamoxifen, Raloxifene or aromatase inhibitor
History of DVT or stroke Do not give tamoxifen
Postmenopausal+osteopenia or osteoporosis Do not give aromatase inhibitor
Postmenopausal women with history of DVT/stroke Aromatase inhibitor
Treatment preference
10 Breast andOncology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Risk reduction therapy
side effects
Treatment Side effect
Tamoxifen Thromboembolic events (stroke, pulmonary embolus, or DVT) and uterine
cancer
Raloxifene Increased risk of thromboembolic events and uterine cancer but to a lesser
extent than tamoxifen
303
Aromatase inhibitors
(Anastrozole, letrozole:
Reversible)
(Exemestane: Irreversible)
Musculoskeletal, primarily joint discomfort, which can be signicant
Loss of bone mineral density
Breast Cancer
Screening and prevention
US Preventive Services Task Force recommends screening mammograms every 2years for women between 50 and
74years of age
American Society of Breast Surgeons, American Cancer Society, and the American College of Radiology
recommends yearly mammography for women with average risk starting at age 40 and stopping when life
expectancy is <10years
For women with a signicant family history of breast cancer, screening should begin 5–10years prior to the
youngest age at diagnosis within the family or at age 35
Women who are known BRCA mutation carriers should begin breast screening at 25years of age with an
annual breast MRI and mammography at age 30
Annual MRI screening is recommended for women with:
• Lifetime risk of breast cancer >20%
• Known BRCA1 or BRCA2 gene mutation
• Untested woman with a rst-degree relative with a BRCA mutation
• Prior chest radiation therapy between the ages of 10 and 30years
• Genetic diseases such as Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome
(or existence of one of these syndromes in rst-degree relatives)
For patients with silicone implants ➔ MRI screening 3years after silicone breast implant placement and
every 2years after that
Screening is not indicated for the reconstructed breast
Genetic testing is now required for all patients with breast cancer
304
Breast cancer types
Types Characteristics
Invasive ductal carcinoma Most common type (70–80%)
Pathology: Hard, gray-white, gritty masses; invade surrounding tissue in an
irregular fashion; stellate shape
Microscopically: Cords and nests of tumor cells with varying amounts of gland
formation
Often associated with an in situ component
S. C. Wimann et al.
Inltrating lobular
carcinoma
Tubular carcinoma (2%) Well-formed tubular structures that inltrate the stroma
Mucinous carcinoma
(2%; older patients)
Medullary carcinoma
(1–10%)
Metaplastic carcinoma Well-circumscribed tumors that contain combinations of poorly differentiated
Second most common type (5–10%)
Pathology: no mass lesion is grossly evident in majority of cases.
More likely to be mammographically occult
Microscopically: small cells that inltrate the mammary stroma and adipose tissue
The abnormal cells often grow in a target-like conguration around normal breast
ducts
More often➔ multicentric and ER +
Low grade, and the cells composing the tubules tend be cuboidal or columnar with
atypical cytoplasmic protrusions
Gelatinous appearance and are well circumscribed
Microscopically➔ nests of tumors cells that are dispersed in pools of extracellular
mucus.
Gross: well circumscribed; often tan in color + areas of hemorrhage or necrosis
Microscopically: poorly differentiated, high-grade tumor cells that grow in a
syncytial pattern and have a signicant lymphoplasmacytic inltrate
ductal adenocarcinoma, mesenchymal, and epithelial components
Rarely node positive
Poor prognosis because of a high risk of metastatic disease
Adenoid cystic carcinoma Identical to adenoid cystic carcinomas that are found in the salivary glands
Favorable prognosis
Micropapillary carcinoma Particularly aggressive
Metastasize to the lymph nodes early in their clinical course
Subtypes of breast tumors
Type Characteristic Prognosis
Luminal A
tumors
ER+; HER2 –
Begins in the luminal lining of the mammary
ducts
70% of all breast cancers
Best prognosis
Lowest recurrence rates
10 Breast andOncology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Subtypes of breast tumors
Type Characteristic Prognosis
305
Luminal B
tumors
Triplenegative
(basal) tumors
(TNB)
HER2+
(Herceptin
receptor)
tumors
Breast cancer
Risk
Begins in the luminal lining of the mammary
ducts
ER+; HER2-
Unlike luminal A tumors, luminal B tumors tend
to be diagnosed in young patients
10–15% of all breast cancers
ER-, PR-, HER2-
Younger patients and are aggressive/ African
American/Hispanics
Associated with BRCA1 mutations
10–15% of all breast cancers
Invasive ductal Ca+necrosis or pushing borders
Genetic counseling for TNB age<60
Fast growing
Positive lymph nodes usually
Worse tumor grade
5–10% of breast cancers
Breast cancer risk in USA is 1in 8 women (12%)
Screening decreases mortality by 25%
Mammographic ndings:
microcalcications, new areas of increased
density, areas of architectural distortion,
irregularly shaped white patch or mass with
spiculated edges
Worse tumor grade, larger tumor size, and
positive lymph nodes
Higher local recurrence after BCT or
mastectomy
Neoadjuvant➔ 50% response/no survival
benet
Poorer short-term prognosis when
compared with HER2 negative tumors
Outcomes have improved with use of
HER2- targeted therapies
When mammographic abnormality is found
Diagnosis
➔ tissue diagnosis with CNB via
mammographic or ultrasound guidance
If lesion is too posterior, not well dened
on imaging, or is located just posterior to
the nipple-areolar complex ➔ surgical
biopsy
MLO and CC views of the left breast
demonstrate a 3.9cm spiculated high
density spiculated mass (arrow)
306
S. C. Wimann et al.
BI-RADS classication and examples
Category Denition Example
BI-RADS 0
BI-RADS 1
BI-RADS 2
BI-RADS 3
BI-RADS 4
BI-RADS 5
BI-RADS 6 Known biopsy- proven malignancy
Incomplete assessment ➔ need additional imaging
evaluation (such as a diagnostic mammogram or
ultrasound) or prior mammograms for comparison
Negative➔ routine screening
Benign ndings ➔return to normal screening
mammograms
Probably benign ndings (<2% malignancy)➔ a
diagnostic mammogram every 6months for
1–2years is necessary➔then normal screening
mammograms if the lesion is stable or resolves
Suspicious for malignancy (2–95% malignant) ➔
tissue biopsy
Highly suggestive of cancer (>95% malignancy) ➔
tissue biopsy
• Cyst on mammogram
• Abnormalities detected on
screening mammography
Complex cysts ➔ CNB
Staging of breast cancer
T N M
Tis: Carcinoma in situ N0: No lymph node involvement M0: No distant metastasis
T1: ≤2cm
N1: Micrometastases or metastases in 1–3 LN M1: Distant metastasis
T2: >2cm but ≤5cm
T3: >5cm N3: >10 lymph nodes or infraclavicular lymph nodes or
T4a: Chest wall
involvement
T4d: IBC
N2: 4–9 lymph nodes
ipsilateral internal mammary lymph nodes
Management of breast cancer
Category Stage Management 5- year survival
Early stage Stage I (T1N0) Primary surgery (BCT or mastectomy)
Stage IIA (T1–2N0)
Stage IIB (T2N1)
to the breast and regional nodes
+/−radiation therapy
Exception: HER2-positive or
triple-negative disease may be treated
with neoadjuvant therapy rst,
followed by surgery
93%
10 Breast andOncology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Management of breast cancer
Category Stage Management 5- year survival
Stage IIB (T3N0)
307
Locally
advanced
Metastatic
disease
Stage III A (T0–1N2; T3N1–2)
Stage IIIB (T4N0–2; T3N1–2)
Stage IIIC (any T, N3)
Stage IV Chemotherapy 27%
Neoadjuvant systemic therapy
followed by modied radical
mastectomy (MRM) +/− RT
85%
Axillary lymph nodes management
Risk of metastases to the axillary lymph nodes is related to the tumor size, location, and histologic grade ➔surgical
evaluation of the axillary nodes depends on whether axillary involvement is suspected prior to surgery
Node status Diagnosis Findings Management
Clinically suspicious/indeterminate
axillary nodes
Clinically normal axillary nodes
Macrometastasis ALND
➔axillary U/S+biopsy
of lymph node
➔SLNB
If biopsy is positive
If biopsy is negative
< 3 LN positive
>3 LN positive
➔ALND
➔SLNB
➔no ALND
➔RT must be given
➔ALND
Research
References Findings
ACOSOG Z0011 trial: Giuliano AE, Ballman KV,
McCall L, etal. Effect of axillary dissection vs no
axillary dissection on 10-year overall survival among
women with invasive breast cancer and sentinel node
metastasis. JAMA. 2017;318(10):918
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
NSABP B-18 trial: Fisher B, Brown A, Mamounas E,
etal. Effect of preoperative chemotherapy on localregional disease in women with operable breast cancer:
ndings from National Surgical Adjuvant Breast and
bowel project B-18. J Clin Oncol. 1997;15(7):2483–2493
Axillary nodal dissection:
For T1–2 tumors with no palpable lymph nodes being
treated with BCT
➔ If <2 positive sentinel lymph nodes➔ no need for
ALND
Breast cancer margins:
No ink on tumor is the current standard for adequate
margins in invasive breast cancer in the setting of
multimodal treatment
Preoperative vs postoperative chemotherapy:
No difference in survival (overall or disease specic) or
local ipsilateral breast recurrence between patients who
received preoperative chemotherapy versus
postoperatively
Increased rates of BCT with the use of neoadjuvant
therapy
308
S. C. Wimann et al.
Indications for radiation therapy
Radiation
therapy BCT Mastectomy
Radiation to
breast
Nodal radiation
Recommended to all patients (decrease
inlocoregional recurrence and improvement in
survival
1–3 positive ALN ➔ strong consideration for Rx
≥ 4 positive ALN ➔ radiation recommended
Neoadjuvant therapy indications and benets
Neoadjuvant
therapy
Indications
Endocrine
therapy Chemotherapy
Hormone receptor–
positive breast cancer
should undergo
endocrine therapy
Patients with cancers with
high-risk characteristics
including
• High-grade tumors
• Tumors >2cm
• Positive axillary lymph
• High 21-gene recurrence
• TNB if the tumor
Neoadjuvant chemotherapy
may render previously
inoperative tumors operative
Tumors >5cm
>4 positive lymph nodes
Involvement of the surgical margins
1–3 positive ALN ➔ strong consideration
for Rx
≥ 4 positive ALN ➔ radiation
recommended
HER2- directed
therapy
HER2-positive breast
cancers ➔ adjuvant
chemotherapy + HER2directed therapy
nodes
score
>0.5cm
Benets
It improves rates of BCT,
minimizes the extent of
axillary surgery
Complete pathologic
response rates are highest for
TNB followed by HER2positive cancers
These rates are least for
hormone receptor–positive
cancers
10 Breast andOncology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Multigene expression models for breast cancer
The Oncotype DX 21-gene recurrence score is a validated prognostic assay that can assist
with identifying patients who are both the most likely and least likely to benet from
adjuvant chemotherapy➔ identies patients that can be treated effectively with endocrine
therapy
309
Oncotype DX
Indications: Node negative, ER-positive, HER2-negative breast cancers who will undergo
a 5-year course of endocrine therapy
This assay is based on a mathematical formula that evaluates 16 genes and 5 reference
genes
The formula predicts the risk of a cancer recurrence with or without tamoxifen therapy
Research
Reference Findings
National Surgical Adjuvant Breast and Bowel
Project (NSABP) B-06 trial: Fisher B, Anderson
S, Bryant J, etal. Twenty-year follow-up of a
randomized trial comparing total mastectomy,
lumpectomy, and lumpectomy plus irradiation
for the treatment of invasive breast cancer. N
Engl J Med. 2002;347(16):1233–1241
Paget Disease
Paget’s disease
Women with stage I or II invasive breast cancer had no
difference in disease-free survival, distant disease-free
survival, and overall survival 20years after receiving either
lumpectomy, lumpectomy and radiation, or total mastectomy
Accounts for 1–4% of all breast cancers
Characteristics
Presentation
Diagnosis
90% of cases are associated with an underlying in situ or invasive carcinoma
Cause by migration of neoplastic cells from the cancer to the nipple via the ductal system
Nipple-areolar skin changes (eczematoid changes, crusting, scaling, or ulceration)➔most
common presentation
Skin changes start at the papilla and then spread to the areola
Patients often report nipple itching
Full-thickness nipple-areolar incisional breast biopsy ➔biopsy reveals Paget disease (large cells
with pale cytoplasm and prominent nucleoli involving nipple epidermis)
Patient with symptoms of Paget disease + no palpable abnormal ndings ➔ mammogram +
breast ultrasound ➔ if negative ➔ breast MRI
If any radiographic abnormalities are identied ➔ image-guided CNB
Patients have DCIS or ductal Ca in breast (85%)
310
Paget’s disease
Treatment Case Management
S. C. Wimann et al.
Paget disease
of nipple
+multicentric
disease
Paget disease
of nipple +
disease
conned to
central breast
Paget disease
of nipple +
high-grade
DCIS conned
to central
breast
➔Mastectomy + SLNB
➔BCT+ SLNB + RT
➔central partial mastectomy+ SLNB+ RT
or
➔Mastectomy + SLNB
Inammatory Breast Cancer
Inammatory breast cancer
Incidence ranging from 0.5 to 2% in USA
Characteristics
Diagnosed at a younger age than all other forms of breast cancer
Incidence higher in African American women
Presentation Breast pain, breast warmth, erythema, edema, p’eau orange, and rapidly growing breast lump
(mimic an infectious process)
Dermal lymphatic invasion by tumor cells
Pathology
Invasive ductal histology (86%)
High incidence of lymph node involvement and metastatic disease at presentation
10 Breast andOncology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Inammatory breast cancer
Diagnostic mammogram on affected side and
screening mammogram on contralateral
side+ultrasound of the breast and regional
lymph nodes+full- thickness skin biopsy
containing both diseased and normal skin
Mammographic ndings: Tumor mass, a large
area of calcication or parenchymal distortion,
and skin thickening
311
Diagnosis
Staging/
grading
Treatment
Survival
MRI➔ to assess extent of disease, chest wall
involvement, skin enhancement, and internal
mammary as well as axillary lymph nodes
If a mass is present ➔ CNB of the tumor
PET–CT to evaluate for metastatic disease or
CT of the chest/abdomen/pelvis and bone scan
MLO mammogram of the right breast
demonstrates diffuse skin and trabecular
thickening, which is highly consistent with
inammatory breast carcinoma.
IBC is classied as ➔ T4d
Patients presenting with IBC are staged as IIIA, IIIB, IIIC, or IV based on tumor biology and the
nding of metastatic disease at presentation
Neoadjuvant chemotherapy (Anathracycline+Taxane) and HER2 targeted therapy (if
HER2 positive) ➔ MRM➔ adjuvant chemoradiotherapy
BCT contraindicated/ SLNB contraindicated/ skin sparring or nipple sparring mastectomy are
contraindicated
Delayed reconstruction can be considered
Stage IV disease ➔ surgical resection of breast primary is not recommended (except if local
control in the setting of skin breakdown)
Very aggressive➔ median survival 36months
Breast Cancer inPregnancy
Breast cancer in pregnancy
Characteristics Becoming more common as maternal age of rst birth continues to increase
Diagnosis
Management
Ultrasound ➔ initial imaging modality
Diagnostic mammography with fetal shielding ➔may be necessary
Pregnant patient + biopsy-proven breast cancer ➔ BCT or Total mastectomy
Pregnant patient in second or third trimester: Can be given neoadjuvant chemotherapy ➔
then after delivery: BCT+RT
Axillary staging surgery:
Clinically node negative ➔ SLNB with technetium-99 (methylene blue dye is
contraindicated)
Clinically node positive➔ ALND
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