Breast Flashcards
(129 cards)
1
Q
1) Early breast cancer is defined as:
2) St Gallan’s definition of low risk:
A
1) Limited to breast and axilla
2) Age >35, AND Node -Ve AND T<=2cm AND no LVSI/peritumoral vascular invasion AND ER/PR expressed AND no HER2/neu amplification/overexpression
2
Q
St Gallan’s intermediate risk group features:
A
1) Int Risk NODE -Ve &1 OR more of the following:
Age <35, T>2cm Gr II/III, Extensive LVI, ER and PR absent, HER2/neu amplification/overexpression
2) Int Risk NODE +Ve (1-3) & ER/PR expression AND no HER2/neu amplification/overexpression
3
Q
St Gallan’s high risk group features:
A
1) Node + ve (1-3) AND lack of ER and PR, OR HER2/neu amplification/overexpression
OR
2) 4 or more nodes +Ve
4
Q
“non-genetic” Risk Factors for breast cancer:
A
1) Estrogen Exposure: Female gender, older age, early menarche, nulliparity, older age at first birth
(>30 years), lack of breastfeeding, late menopause (>55 years), hormone replacement therapy.
2) Lifestyle/Exposure: High-fat diet, postmenopausal obesity, sedentary lifestyle.
3)Personal History of Breast Disease: Prior breast cancer, DCIS, LCIS, atypical ductal hyperplasia.
4) dense breast tissue.
5) history of RT during youth (age <30 years).
5
Q
Describe how risk of BrCa changes with increasing family Hx.
Key High risk genes:
A
1) Family History: Risk increases with more first-degree relatives.
2 ) Genetics (5%–10% hereditary):
BRCA1 (17q21)
BRCA2—(13q12)
Li–Fraumeni—AD (17p), p53,
Cowden syndrome—AD (10q23), PTEN,
ATM;
Peutz–Jeghers.
6
Q
Site of chromosomal abnormality of BRCA 1 &2
Normal role of these genes
A
BRAC1 = 17q21
BRAC2 = 13q12
Normal function in DNA repair: Homologous recombination, crosslink repair, and protection of stalled repair sites.
Leading to cell survival and genomic integrity.
7
Q
Contribution of genetics to BrCa risk:
Describe the BRCA 1 cancer risks:
Describe the BRCA 2 cancer risks:
A
Genetics (5%–10% hereditary):
BRCA1—AD (17q21), 60% to 80% lifetime risk of breast cancer, 30% to 50% lifetime risk of ovarian cancer, higher risk of triple negative (ER−/PR−/HER2−);
BRCA2—AD (13q12), 50% to 60% lifetime risk of breast cancer
10% to 20% lifetime risk of ovarian cancer, male breast cancer, prostate, bladder, endometrial, and pancreatic ca.
8
Q
Describe the BRCA 2 cancer risks:
A
BRCA2—AD (13q12), 50% to 60% lifetime risk of breast cancer
10% to 20% lifetime risk of ovarian cancer, male breast cancer, prostate, bladder, endometrial, and pancreatic ca.
9
Q
Describe the glandular tissue of the breast.
With reference to this, outline the both the most, and the least common sites of cancer:
A
Glandular tissue is arranged in 15 to 20 lobes with a system of lactiferous ducts that open at the nipple.
UOQ contains the greatest volume of glandular tissue (most common location of breast cancers).
The least common location is the lower inner quadrant.
10
Q
Very simple description of the location of axillary node levels I, II and III
A
Relative to pec minor which inserts into the corocoid process of the scapula:
Levels I = inferolateral,
II = Deep
III = superomedial to pectoralis minor
11
Q
Where is Rotter’s?
A
Between pec maj and min (anterior to level II).
12
Q
Anatomical location of IMN:
Frequency of node +ve tumours draining to this site
A
IMNs are situated along IM vessels adjacent to sternum in the 1st 3 intercostal spaces, ~2 to 3 cm lateral to midline, and 2 - 3 cm deep.
Approx 30% of medial tumors and 15% of lateral tumors drain to the IMN.
13
Q
Fill in the gaps:
ER and/or PR are expressed in X% of tumors (more common in ?).
HER2/neu (c-ERbB-2 or human epidermal growth factor receptor 2) is a ______ ________ _______, with HER2 amplification seen in Z% to Y% of invasive cancers.
Trip -ve occurs in ~W% of cases and more commonly
found in _____ mutation carriers.
A
ER and/or PR are expressed in 70% of tumors (more common in postmenopausal
patients).
HER2/neu (c-ERbB-2 or human epidermal growth factor receptor 2) is a receptor tyrosine kinase, with HER2 amplification seen in 25% to 30% of invasive cancers.
TNBC occurs in ~15% of cases and more commonly
found in BRCA mutation carriers.
14
Q
Differentiate between N1, N2, and N3 breast cancer
A
cN1 = moveable level I or II ipsilateral nodes
cN2 = Fixed
cN3 = Level III nodes or SCF or IM + level I &/or II
15
Q
Key pathological features of Invasive ductal carcinoma:
A
80% cases. Often well seen on mammogram. Firm mass with desmoplastic reaction, invades through basement membrane, solid
cords of cells.
Invasive carcinoma with evidence of mammary epithelial origin either by morphology or immunohistochemistry
Diagnosis of exclusion, lacks the histologic features to classify morphologically as a special subtype of breast cancer.
Desmoplastic reaction to tumor = the growth of fibrous connective tissue around tumor cells
16
Q
Key pathological features of Invasive lobular carcinoma:
A
10 to 15% of cases overall, more common in women 45-55, estrogen exposure appears a greater risk factor (e.g. HRT),
CDH1 mutation increase risk of lobular but not ductal cas,
BRAC2 increases risk of both : rubbery texture, poorly visible on mammogram (better w/ MRI).
“Indian filing” histology,
Often bilateral/multicentric,
>80% ER+,
spreads to unusual locations such as meninges, serosal surfaces, BM, ovary, and RP - ?WHY????
17
Q
Example of in-situ hybridisation test for breast cancer
A
HER2 status into absent, equivocal or present (0-1, 2+, 3+) based on IHC and FISH single probe (for gene copies, >= 6 suggests +ve) and double probe for ratio Her2:CEP17 where >=2 suggests Her2 +ve
What does CEP17 mean?
CEP17 stands for chromosome enumeration probe 17, which means that the cancer cells have more than one chromosome 17
18
Q
Examples of some DNA microarray tests in breast cancer
A
Of prognostic value, only Oncotype Dx has validation for prediction and can be potentially beneficial in identifying low-risk patients not requiring CTX.
Oncotype Dx - 21 gene array (16 cancer genes and 5 controls). The current on
Mamma Print (Amsterdam-70) - RCT prognostic validation - despite clinical high risk, low genomic risk pts have 95% distant met free survival without chemo
19
Q
Some gene profiling models for breast cancer:
A
Amsterdam 70-gene good-versus-poor outcome model (low signature vs. high signature),
The 21-gene recurrence score model (Oncotype Dx)
Intrinsic subtype model
20
Q
Why was oncotype DX developed:
Key finding for 1 group in this study
A
The 21-gene recurrence score (Oncotype DX) was developed for pts w/ LN-negative, ER+ BrCas, receiving tamox ± CHT on NSABP B-14, and is stratified into low risk (<18 score), intermediate risk (18–30), and high risk (>30) of recurrence in order to estimate the relative benefit of CHT in addition to hormonal therapy.
Rates of distant recurrence in the low-risk, intermediate-risk, and high-risk groups were 6.8%, 14.3%, and 30.5% at 10 yrs. TAILORx found noninferiority of endocrine therapy alone over endocrine + CHT in women w/ int risk (score of 11–25)
21
Q
NZ screening guidelines for general population.
Compare (if you can be bothered) to the
A
Mammo every 24 months if:
1) Aged 45 – 69 years (in Aust women 40-50 can ask and get)
2) no sx of breast cancer
3) not had a mammogram in the last 12 months
4) not pregnant or breastfeeding
USPSTF: Biennial screening for age 50 - 74,
- no routine screening for 40 to 49 (self-ex controversial).
- High-risk women should begin screening 10 years before age of youngest first-degree relative diagnosed.
- Insufficient evidence for benefit/harm of clinical exam; however, recommended against teaching breast self-examination.
22
Q
Evidence for breast screening in elderly women
A
There is no evidence that regular breast screening reduces the rate of deaths from breast cancer in women over 75 years.
This does not apply to:
- Pt w/a mother or sister who had brCa before menopause or developed bilat cancer
- Prev breast cancer
- Prev Bx of breast tissue showing an ‘at-risk lesion’.
23
Q
Benefit of breast screening program
A
Evidence suggests that for women >=50, risk of death from brCa is reduced by ~1/3 with 2 yearly mammograms. In women 45 - 50 yrs, the risk of death from brCa is reduced by a 1/5 with reg mammography.
24
Q
Evidence for general BrCa screening before age 45
A
The false positive rate (due to lower incidence and more importantly dense breast tissue causing poorer scan and higher frequency benign lesions) is high and leads to unnecessary invasive investigations,
25
Which younger women (define younger) may benefit from screening? - what is the general advice?
For women ages less than 45, (ACS) indications are:
Screen at 25 to 30 y/o for BRCA mutation carriers and untested first-degree relatives of carriers;
Screen 8 years after or at 25 y/o (whichever is later) for women who received mantle RT/thoracic
RT between 10 and 30 y/o.
Screen annually for women with biopsy-proven lobular neoplasia, atypical ductal hyperplasia, or personal history of breast cancer beginning at diagnosis, but not
when <30 y/o.
26
Evidence for self Exam:
Meta and RCT show no diff in size or stage of BrCa at Dx or in the number of deaths from BrCar for women taught to use a systematic approach for breast self-examination vs those who did not receive instruction. Trials were in Russia and China and involved large numbers. While applicability for Australia/NZ has been questioned.
A UK study of over 63,000 women 45–64 has shown no difference in the number of deaths from breast cancer after 16 years of follow-up.
27
For women at high risk of breast cancer and age <50 what should be considered
Bilateral breast MRI screening (funded by medicare).
ACS guidelines: screening MRI for women with 20- 25% or greater lifetime risk of BrCa, including women with hereditary mutations (BRCA, Li–Fraumeni, Cowden), strong FamHx of br/ovarian ca, and women who received prior thoracic RT for Hodgkin’s disease before age 30
28
On Hx a breast mass is less concerning for malignancy if?
Is less concerning if associated with changes in menstrual cycle.
29
The "benefit" of whole breast irradiation following BCS for early breast cancer:
Large population Prevalence statistics and meta analysis of numerous RCT trials suggests: WBI after BCS improves LR rates (from 26% to 7% at 5 years about a 2/3 reduction) and OS by 5% at 15 years.
"Cancer treatment and survivorship statistics, 2019"
Older meta-analysis (2014) suggests that for post menopausal women on systemic therapy (mostly Tamox), with ER+ve, node -ve, <=T2, an NNT of 24 to prevent 1 recurrence.
30
The most common histologic scoring system for determining breast cancer grade:
Nottingham Histologic Score system (also termed “the Elston-Ellis modification of Scarff-Bloom-Richardson grading system” modified SBR)
31
Broad outline of Nottingham Histologic Score system
Each of the 3 features graded 1-3:
1) Amount of gland formation (how well cells differentiate into normal glands, e.g >75% gland = grade I)
2) Nuclear features (degree of pleomorphism, e.g vesicular nuclei + prominent nucleoli + marked nuclear variation in size and shape = grd 3)
3) Mitotic activity/ 10HPF (grd 1 =<7 & grd 3>16)
The final total score (range 3-9):
Grade I tumors have a total score of 3-5
Grade II tumors have a total score of 6-7
Grade III tumors have a total score of 8-9
32
Cystosarcoma Phyllodes - risk factor, cell origin, histo, and grading.
Linked w/ Li-Fraumeni (p53 tumour suppressor gene) syndrome (SBLA)
Origin is stromal cells
Fibroepithelial, “leaf-like" (Phyllode is Greek for leaf) large, encapsulated tumors, usually benign
w/o invasion.
Classified into: benign, borderline and malignant grade. Based on stromal cellularity, atypia, mitotic count, stromal overgrowth, and the nature of tumour borders.
33
For SBLA syndrome, what does SBLA stand for
- Sarcomas
- Breast cancers (breast Ca before age 40 most common clinical presentation in females).
- Leukaemia
- Adenocortical carcinoma (almost pathognomonic)
Also primary brain, especially GBM (13%)
34
Relative incidence, clinical and pathological features of Lobular carcinoma:
5 to 10% of cases
Rubbery texture, less visible on mammogram
(better imaged with MRI),
“Indian filing” histology, often bilateral/multicentric, >80% ER+, spreads to unusual locations such as meninges, serosal surfaces, BM, ovary, and RP.
35
Name some rarer subtypes of breast cancer:
In general what histological criteria needs to met to allow such a Dx?
Need >90% Predominant Pattern:
1) Tubular—small, well-differentiated variant of IDC, >75% tubules (think SBR score), usually ER+/PR+.
2) Medullary—aggressive subtype of IDC a/w BRCA1, presents at younger age (<50), LNs are large/hyperplastic, most are triple negative. Appear lobular or nodular with foci of hemorrhage, often necrosis, and cystic degeneration
3) Mucinous/colloid—older patients, favorable.
4) Papillary—older patients, often multifocal/diffuse, often LN+ even when small size.
5) Cribriform—ER+/PR+.
Other uncommon variants include metaplastic (poor prognosis), squamous cell, invasive micropapillary, adenoid cystic, mucoepidermoid, secretory, apocrine, spindle cell, lymphoma, neuroendocrine small cell, and clear cell.
Mammary carcinoma is a mixture of invasive ductal and lobular carcinoma.
36
Features of mucinous and papillary breast carcinoma
1) Mucinous/colloid—older patients, mucinous component that comprises > 90% of tumor, ER and PR hormone receptor positive and HER2 negative (luminal A subtype), favorable prognosis.
2) Papillary—Rare subtype of IDC, older patients, often multifocal/diffuse, invasive papillary growth.
37
What is EIC? Definition?
What is its significance?
Extensive Intraductal Component: Defined as ≥25% DCIS within the invasive carcinoma specimen and extending beyond edges
of tumor.
Was identified as a risk factor for LR after BCT, but no longer considered the case provided margins are negative. (But think TROG 2022 DCIS boost study..)
38
Describe Paget's disease of breast:
Chronic eczematous changes of the nipple–areolar complex, with underlying intraepidermal adenocarcinoma of the nipple (in 95%). About 50% have a palpable mass (>90% are invasive cancer) and 50% have no mass (typically DCIS).
Low risk of axillary nodal mets.
39
System for describing breast lesions on imaging:
BI-RADS
0 = incomplete imaging
1= Negative (<%1 risk malig)
6= Bx proven malignancy
40
Initial work-up (Hx and Ex) of a breast lump:
Full Hx&Ex:
Hx:
- Duration/1st noticed, growth, tenderness, size/Symptom relation to menstrual cycle.
Risk Factors: age, Fam Hx (1st degree relatives) previous Hx of cancer or thoracic radiation age <30.
Estrogen exposure (e.g. nullparity, age>30 1st child, HRT ect). EtOH, obesity/sedentary lifestyle.
Ex: full bilateral breast and nodal (Ax+SCF) - see other slide
41
Non-malignant DDx for a breast lump:
1) Fibroadenoma (solitary mass, well defined, mobile)
Cysts (more diffuse and less firm, suspicious if blood in aspirate or contents reaccumulate quickly);
2) Infection (mastitis or abscess);
Mondor’s cord (thrombophlebitis of superficial breast veins);
3) Fat necrosis;
4) Intraductal papilloma (common cause of bloody discharge);
5) Sclerosing adenosis (nodular benign condition consisting of hyperplastic lobules of acinar tissue);
6) lactocele.
7) Phylodes tumour
42
The Intrinsic Subtype Model of genetic risk suggests that their are X intrinsic sub stypes. What are they?
There are four main intrinsic subtypes (in order of risk):
Luminal A (best prognosis),
Luminal B,
HER2 enriched (HER2+), and
Basal-like (worst prognosis)
43
A 55yro woman presents with a 1 month Hx of a ~2cm firm/rubbery breast lump. Nil other concerning features on Hx and Ex. What further workup?
Bloods: LFT/alk phos (indicated distant disease) + RFTs (for suitability for systemic options).
Mammogram and uss (+/-Bx) are typical 1st steps.
Systemic staging workup is not routinely indicated per NCCN for anatomic stages I to II in the absence of suspicious symptoms, physical exam findings, or lab abnormalities (e.g., elevated alk phos or LFTs).
If suspicious, studies may include PET/CT or CT CAP and bone scan, ± MRI brain.
44
How are mammogram orientated?
Key indicator of study quality?
Key concerning findings?
On CC view, the lateral edge of the film is typically marked by “CC” marker. On MLO view, assess for image quality by ensuring pectoralis muscle is included. Concerning mammographic findings:
calcifications 100 to 300 microns,
>10 clustered linear calcifications,
spiculated lesions.
45
Role of USS in Ix of a breast lump:
Determine solid vs. cystic masses (not useful for calcifications) and evaluate nonpalpable masses identified on mammogram.
46
Compare mammogram to MRI for screening:
Possible indications for MRI:
Higher sensitivity (>90%) than mammography, but lower specificity (39%–95%) due to false
positives. Suspicious features for malignancy: strong, rapid contrast enhancement, spiculated margins, rim enhancement, heterogeneous appearance.
Possible MRI Indications:
Obscured breast (silicone implants), suspicious masses w/ -ve mammogram and uss,
evaluation of poorly imaged tumors such as ILC or DCIS without microcalcifications, or pts presenting with positive axillary nodes of unknown primary (MRI detects primary tumor 80%–90% of the time).
47
The utility of MRI prior to breast conservation surg:
MRI can change surgical management in 25% of cases but does not reduce +ve margins, re-excision rates, or LR rates.
48
Prognostic factors in early breast Ca
LN+ (strongest factor), young age, ER/PR
negativity, HER2/neu amplification (in the absence of HER2-directed therapy), high grade, LVSI+,
basal-like subtype
49
Predictive factors in early breast cancer:
Identification of clinically useful predictive markers has not been as successful as the identification of prognostic ones. Factors that predict response to directed therapies:
ER is probably the most powerful predictive marker (both in determining prognosis and in predicting response to HTs). The value of PR is less well established.
HER2 status - for HER2 directed therapies.
Oncotype 21 - int and high risk benefit from CHT in addition to hormone therapies.
Tumor infiltrating lymphocytes — there is a correlation between the extent of lymphocytic infiltration in the tumor or surrounding stroma, and chance of achieving complete path response with neoadj CT, particularly in HER2-ve and trip-ve
50
Types and role of different Bx techniques used to Ix a breast lump
1) Core Bx (see below)
2) Needle aspirate (if cystic on ultrasound).
3) FNA may detect abnormal cells, but cannot distinguish DCIS from IDC and cannot identify ER/PR/HER2 status.
As such core bx preferred:
USS core bx for palpable masses.
Stereotactic core bx or needle localization if nonpalpable lesion with suspicious calcifications.
MRI-guided biopsy if only visible on MRI.
Punch biopsy for Paget’s or if suspicious of dermal involvement (e.g., suspected inflammatory breast
cancer).
51
Criteria for T1 - T4 brCa tumour grade:
T1 (≤2cm): a=0.1-0.5, b>0.5 and ≤1cm, c = >1 cm and ≤2cm.
T2: >2 cm and ≤5cm
T3: >5 cm
T4a: Extension to chest wall (EXCEPt pec MAJ)
T4b: Peu d'orange
T4c = a+b
T4d = Inflammatory brCa
52
Name the mastectomy options:
1) Radical mastectomy: currently no absolute indications for this procedure.
2) Modified radical
3) Total mastectomy Removal of breast tissue only (preservation of both pectoralis muscles and axillary
lymph nodes).
4) Skin-sparing mastectomy = Resection of biopsy scar and/or skin immediately overlying the tumor, and removal of breast parenchyma.
5) Nipple-sparing mastectomy Skin-sparing mastectomy with preservation of the nipple–areolar complex.
6) Lumpectomy or partial mastectomy
53
The impact of margins of resection on the risk of local recurrence:
Involved or close pathological margins after breast conserving surgery for early stage, invasive breast cancer are associated with increased distant recurrence and local recurrence
54
Indications for adj chemo for early breast cancer?
Evidence for timing?
Typically given pre- or post-op to LN+ patients, ER−, HER2+, and women with multiple adverse features (e.g., young age or high Oncotype DX scores).
Neoadjuvant CHT has equivalent survival as adjuvant (NSABP B-18) but may allow for less extensive surgery.
A trial investigating whether adj CTx should precede RT (Recht Trial) initialy demonstrated lower LR rates in chemo 1st group - however LR curves converged at a later time point.
55
Indications for adj chemo for early breast cancer?
Evidence for timing?
Typically:
LN+ ve,
ER−,
HER2+,
and pts with multiple adverse features (e.g., young age <40 or high Oncotype DX scores).
Neoadjuvant CHT has equivalent survival as adjuvant (NSABP B-18) but may allow for less extensive surgery.
Virtually all subgroups of women have a benefit in DFS from adjuvant CHT, benefit most pronounced in younger, LN+, and ER− patients.
Note: Role of CHT is unclear in women >70 y/o because this age group was excluded from early clinical trials.
56
For Early Breast cancer, the optimal timing of the commencement of endocrine therapy (anastrozole) in relation to radiation therapy is currently under investigation in the ??? Trial
Can trastuzumab be given concurrently w/XRT?
For Early Breast cancer, the optimal timing of the commencement of endocrine therapy (anastrozole) in relation to radiation therapy is currently under investigation in the STARS Trial
Anti HER2 therapy may be given concurrently with radiation therapy
57
Indications of breast boost - name who recommends?
ASTRO (2018) Guidelines:
50 years or younger with any grade tumor, or in patients aged 51 to 70 years with high-grade tumors or positive margins.
***Consistent w/subgroup analysis of Bartelink (now 20yrs) - suggests greatest benefit age<50. Also those w/adjacent DCIS (at long term follow up) and grdIII
58
Studies of breast boost are typically based on what dose?
General evidence of benefit?
16Gy/8# - 10Gy/5# is way more common.
Bartelink and "Lyon Study" - Improves LC, no change OS, increased fibrosis (the later not clear in Lyon).
Subgroup analysis of Bartelink suggests greatest benefit age<50. Also those w/adjacent DCIS (at long term follow up) and grdIII
59
Role of Trastuzumab?
Known issues?
Complementary with what other drug?
Trastuzumab has OS advantage for HER2+ patients in addition to cytotoxic CHT.
Trastuzumab is not given concurrently with Adriamycin because of cardiotoxicityconcerns, but is safe to give with RT. Trastuzumab-related cardiac effects are reversible.
Complementary with pertuzumab
60
Pertuzumab has been added to trastuzumab to provide dual anti-HER2 therapy, which results in?
Pertuzumab has been added to trastuzumab to provide dual anti-HER2 therapy, which results in pCR rates of 50% to 60% in the neoadjuvant setting.
61
Name 2 alkylating chemotherapies:
Cyclophosphamide (boob)
Tamzolomide (Brain)
62
Name some anthracycline chemotherapy drugs
Adriamycin (Doxyrubicin)
Epirubicin.
63
Common Chemo regimens in early breast cancer include (just list some, no detail - that's another card):
AC = Adriamycin (Doxyrubicin) + cyclophosphamide
AC then T: Adriamycin + cyclophosphamide followed by
paclitaxel (T = Taxane)
AC->TH: same as AC->T, with the addition of trastuzumab concurrent with Paclitaxel, followed by Herceptin monotherapy
TC: docetaxel + cyclophosphamide
64
Common Chemo regimens in early breast cancer include (just list some, no detail - that's another card):
AC = Adriamycin (Doxyrubicin) + cyclophosphamide
AC then T: Adriamycin + cyclophosphamide followed by
paclitaxel (T = Taxane)
AC->TH: same as AC->T, with the addition of trastuzumab concurrent with Paclitaxel, followed by Herceptin monotherapy
TC: docetaxel cyclophosphamide
65
Broadly (very) outline the rationale for chemo and mab therapy choice in local breast cancer:
Anthracycline-based CHT is superior to nonanthracycline-based regimens, and may especially benefit HER2+ patients.
The addition of a taxane has OS benefit for LN+ patients compared to AC alone.
Dose-dense regimens (q2weeks instead of q3weeks) offer OS advantage for high-risk patients.
TC provides OS benefit compared to AC
66
Indication for hormone therapy:
Essentially indicated for all ER or PR +ve cancers, unless a contraindication.
67
MOA for tamoxifen?
For anastrozole:
Tamoxifen is a partial estrogen agonist that functions as a competitive inhibitor.
Anastrozole or letrozole block conversion of androgens
to estrogen in fat, liver, and muscle and are ineffective in premenopausal women (due to ovarian
production of estrogen). Postmenopausal women are typically treated with anastrozole 1 mg daily for
5 years.
68
Typical dose and benefit/disadvantages of an aromatase inhibitor:
Postmenopausal women are typically treated with anastrozole 1 mg daily for 5 years.
Compared to tamoxifen in postmenopausal women, AIs improve DFS and less risk of endometrial cancer and DVT
BUT higher rates of myalgias, arthralgias, and osteoporosis
69
Dose of tamoxifen
Premenopausal pts typically treated with tamoxifen 20 mg daily for 5 years, but10 yrs recently found to further reduce recurrence and breast cancer mortality by approximately 1/3 in the first 10 years and by approximately 1/2 subsequently.
70
Side effects of tamoxifen:
Side effects include hot
flashes, vaginal discharge/bleeding, cataracts, retinopathy, thromboembolic events (1%), endometrial
cancer (RR 2–7), and uterine sarcomas.
71
Absolute contraindications to BCS: .
Persistently positive resection margins after re-excision attempts,
multicentric tumors, diffuse malignant-appearing mammographic microcalcifications,
prior RT to the breast or chest wall,
***inflammatory breast cancer
72
Relative contraindications to BCS:
Pregnancy (can perform BCS in third trimester and defer RT until after delivery), mastectomy preferred in earlier trimesters to decrease likelihood of XRT.
Active lupus/scleroderma,
Large tumor in a small breast (cosmetic outcome may not be satisfactory).
BRCA mutation carriers are not contraindicated to receive RT; however, their risk of developing
new primary cancers remains high after BCT, so bilateral mastectomies are commonly performed.
73
Mastectomy VS breast conservation?
At least six randomized trials have demonstrated no significant differences in OS between BCT and mastectomy
74
What is the role of adj whole breast radiation following breast conservation therapy?
Holland study - 43% of unifocal cancers in mastectomy specimens had tumor foci >2 cm from the index lesion.
NSABP B-06 showed a 1/3 reduction in LR at 20yrs
The EBCTCG meta-analysis was large enough to demonstrate that adjWBI improves survival. RT decreased 15yr risk of death from 31% to 26% for LN− patients (5% decrease) and 55% to 48% for LN+ (7%).
This suggests a “4:1 ratio”—one brCa death avoided by year 15 for every 4 local recurrences prevented by yr5 and for every four overall recurrences prevented by yr 10.
There has been no subgroup (age, grade, size, hormone status), which has not been shown to benefit from RT.
75
Name 4 key early breast nodal irradiation studies:
Mnemonic "ZAME" (suitability for a mnemonic is my criteria for "key"):
Z11 ALND vs WBI and systemic therapy,
AMROS - surgery vs WBI + axilla
MA.20 node+Ve or high-risk node-Ve breast treated w/BCS and adjSystemics: either WBI+ plus RNI (including internal mammary, SCF, and axillary) (nodal-irradiation group) VS whole-breast irradiation alone (control group).
EORTC (22922) node -ve medial/central tumours
76
Name 4 key early breast nodal irradiation studies:
Mnemonic "ZAME" (suitability for a mnemonic is my criteria for "key"):
Z11 ALND vs WBI and systemic therapy,
AMROS - surgery vs WBI (pretty wide axilla field),
MA.20 node+Ve or high-risk node-Ve breast treated w/BCS and adjSystemics: either WBI+ plus RNI (including internal mammary, SCF, and axillary) (nodal-irradiation group) VS whole-breast irradiation alone
EORTC (22922) node -ve medial/central tumours
77
Describe MA.20 RCT:
Notable inclusion?
MA.20 (median follow-up was 9.5 years):
Patient cohort: node+Ve or high-risk node-Ve breast treated w/BCS and adjSystemics:
either WBI+ plus RNI (including internal mammary, SCF, and axillary) (nodal-irradiation group)
VS
Whole-breast irradiation alone
Notably, IM nodes were included.
Found: For node Ve+ or high-risk node-Ve Pts, the addition RNI to whole-breast irradiation did not improve OS but reduced the rate recurrence = 5% improvement in DFS at 10yrs (they talk up the "40% relative risk reduction")(But in general most pts did well so this number is small - pts w/>3 nodes tended to be excluded as they all had radiation- taking away the strength of the signal).
Higher rates of grdII pneumonitis
78
RCTs suggest nodal irradiation increases the risk of
1) Near doubling of the rate of lymphedema following RNI
2) Rate of acute radiation pneumonitis was also significantly higher
There has not been a strong signal for increased cardiac toxicity, however this may occur at greater timescales than those of the studies (e.g. 10yrs)
79
Basic findings of the key nodal irradiation studies:
Z11 (T1-T2cN0 w/1-2 LN+ micro/macro): ALND is not necessary in pts who receive WBI and systemic therapy (and conversely WBI and systemic not needed if ALBD).
AMROS (T1-2cN0): randomized prior to SLNB: If +ve node either completion ALND or 50/25 to the pits= no diff @5yrs. BUT worse lymphoedema w/surg!
MA.20 (T1-T2, N0-N1): 50/25 to nodes vs WBI only - nodal radiation (including IM) decreased breast cancer recurrence (RRR by 40% but on;y 5% in real terms) but not OS.
EORTC (22922) node -ve medial/central tumours (of any type/grd): IMN and medial SCV slight BCM benefit - initial small OS benefit disappears @ 15yrs. Overall suggests benefit of RNI for node -ve central.
80
Does completion ALND after a positive SLNB benefit cN0 patients?
NSABP B-04: not all undissected nodal disease results in recurrence. Several RCTS have since shown similar rates of axillary recurrence and DFS between SLNB and ALND among clinically node-negative patients, most of whom received adj RT.
81
Can RT replace ALND in select cN0, SNBx +ve patients?
The surgery RCTs:
1) "Z11" (Z00011): completion ALND post SLNB offered no improvement vs SLNB alone in SLN+ (1-2 SLN mets) pts receiving BCS + WBI, for both macro/micromets.
Remember these are clinically node neg....
2) AMAROS/EORTC: randomized prior to SLNB: If +ve node either completion ALND or 50/25 = no diff @5yrs.
High-tangent irradiation from Z11 results in similar dose distribution in levels I and II compared to the AMAROS treatment field design in some patients. This supports earlier assumptions that irradiation may have accounted for good results after sentinel lymph node dissection alone in Z11.
82
In cN0 disease but with positive nodes on SLNB, ALND is...?
In cN0 disease but w/+ve nodes on SLNB, ALND is not recommended if pts will receive axillary radiotherapy and systemic therapy = Z0011 and AMAROS. In addition to providing no benefit in survival or recurrence rates, ALND resulted in worse lymphedema and paresthesia.
83
A general conclusion of the AMROS study:
ALND vs.axillary RT after a positive SLNB:
For cN0, snbX +Ve patients, axillary RT provides similar control with less risk of lymphedema compared to ALND.
84
General approach to breast nodal irradiation:
Recommended in:
pT3 N+, pT4 N any, pT any N2/3
Consider for:
pT1-2 N1, pT3 N0 depending upon presence of additional risk factors****.
IMC may be more strongly considered if N2+ and/or medially located tumour(s).
*Additional risk factors for locoregional recurrence include:
Presence of lymphovascular space invasion (LVI).
High tumour grade.
Multifocal or multicentric tumours.
Young age.
ER negative.
Nodal burden.
85
Indications to treat IMC
The independent benefit of IMC coverage as a component of RNI is uncertain.
IMC may be more strongly considered if N2+ and/or medially located tumour(s).
86
The role of regional nodal irradiation in breast conservation pts undergoing ALND?
Post lumpectomy, RNI is indicated for certain high-risk patients, such as those with LN+ and/or ER-negative
disease.
The MA.20 (Nodes vs WBI only) and EORTC 22922/10925 trials showed an improvement in LRR, DM, DFS and a trend toward OS.
It remains an area of controversy which pts may be adequately treated without RNI.
87
Origin of WBI doses:
40.05Gy/15#
26Gy/5#
START B: 40Gy/15 has low 10yr recurrence 4.3% vs 5.5% in 50Gy/25 group
FAST-FORWARD: 40 Gy/15 fx (over 3 weeks), 27 Gy/5 fx
(5/#/week), or 26 Gy/5 fx (5/#/week). Data at 5-years released 2020. 26Gy/5# at 5 years seems equivalent w/trend to better than 40/15, LRR 1.8%.
88
Brief outline of the evolution of dose schedule (hypofractionation) for whole breast radiation:
At least 4 RCTs from UK and Canada support hypofractionation.
- A tendency for reduced LRR in the hypo# groups
- At least for START late toxicity seems equivalent with Hypo.
GOC/RMC (75% of patients had boost in both groups): 43Gy/13 non-inferior to 50Gy/25 - 43Gy/13 10yr LRR ~10%
START A (60% had boost): 41.6Gy/13# non-inferior to 50Gy/25 10yr LRR 6-7%
**START B (~40% had boost): 40Gy/15 has low 10yr recurrence 4.3% vs 5.5% in 50Gy/25 group
FAST (no boost, looked at 1#/week vs conventional including normal tissue effects): NTE rates were comparable between 28.5 Gy/5 fx (19%) but 30Gy/5# worse. All had very low 10yr LRR 1-2%
FAST-FORWARD: 40 Gy/15 fx (over 3 weeks), 27 Gy/5 fx
(5/#/week), or 26 Gy/5 fx (5/#/week). Data at 5-years released 2020. 26Gy/5# at 5 years seems equivalent w/trend to better than 40/15, LRR 1.8%.
89
Justify 26Gy/5#s compared with the established hypo# schedule:
Some notable limitations (arguably 3)?
FAST-FORWARD: 40 Gy/15 fx (over 3 weeks), 27 Gy/5 fx
(5/#/week), or 26 Gy/5 fx (5/#/week). Data at 5-years released 2020. 26Gy/5# at 5 years seems equivalent w/trend to better than 40/15, LRR 1.8%.
Limitations:
1) Very low representation of mastectomy cases (approximately 93% for conservation vs. 6.5% for mastectomy)
2) Boost was “allowed” (not mandatory) to 10–16Gy. Only 25% had boost. ?actual boost strategy to be used.
3) Study says applicable to patients T1-3, N-1, M0. But majority (>70%) pT1 and pN0, with >80% node negative. Therefore applicable only to pT1pN0. This explains very low primary end point events. A large proportion of pts may fit criteria for accelerated partial breast irradiation or be candidates for no adjuvant radiotherapy at all.
90
Pts suitable for FAST-Forward?
Age >50 (age less than 50 included, but under represented)
Study says applicable to patients T1-3, N-1, M0. But majority (>70%) pT1 and pN0, with >80% node negative.
BCS potentially not post mastectomy - arguably under-represented in study (only 7% of Ps).
91
What is the role of IMRT in early-stage breast cancer?
Trial data has focused on older 2D vs IMRT, with no trial to date comparing 3d to IMRT. For 2D IMRT improved dosimetry and was associated with lower acute toxicity, including desquarmation.
Studies looking at dosimetry suggest IMRT reduces mean dose and high-dose volumes of ipsilateral lung and heart compared to 3DCRT, but 3DCRT is superior in terms of low-dose volume.
92
The benefit of WBI following BCS in older post menopausal women with early breast cancer?
Define "older"
Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II):
Small Significant reduction in IBR with XRT - 1·3% (95% CI 0·2-2·3; n=5) in women assigned to whole-breast radiotherapy and 4·1% in the no XRT group at 5yrs
93
Acceptable left-sided plan mean heart dose? relationship of risk relative to dose?
MHD <4Gy, <5Gy acceptable - especially in older patients.
Darby et al: rates of major coronary events (MI, coronary revascularization, death following IHD) after breast RT increased linearly with MHD with no apparent threshold.
In series data using older RT techniques, left-sided brCa pts had higher risk of cardiac mortality BUT Using modern RT, laterality does not seem to influence survival.
94
Role of cardiac-sparing RT techniques?
Rates of major coronary events (MI, coronary revascularization, death following IHD) after breast RT increase linearly with MHD with no apparent threshold.
With the adoption of DIBH and prone positioning, MHD <1 Gy and <2
Gy can be achieved for right and left breast cancers, respectively
95
Typical mean heart dose for:
1) DIBH
2) Prone positioning
1) DIBH = MHD <1G
2) Prone positioning = MHD <2Gy
96
Role of endocrine therapy in BCT?
Key recent study?
Which patients may avoid XRT?
NSABP B-21 showed that adj tamoxifen alone is inferior to RT alone, but together act synergistically to reduce ipsilateral recurrence in low-risk patients undergoing BCT.
Omission of RT may be considered in carefully selected pts w/ T1N0, ER/PR+, HER2−, negative margins, who are older (>65–70 y/o) or with reduced life expectancy, and who are committed to taking 5 years of endocrine therapy (~30%–40% stop endocrine therapy before completion of 5 years).
97
BCS patients in whom RT may be omitted after lumpectomy?
A major limitation of the no RT opton?
Omission of RT may be considered in carefully selected pts w/ T1N0, ER/PR+, HER2−, negative margins, who are older (>65–70 y/o) or with reduced life expectancy, and who are committed to taking 5 years of endocrine therapy.
~30%–40% stop endocrine therapy before completion of 5 years!!!
98
Any role for intraoperative RT for early breast cancer (give some positives and negatives):
Two large prospective randomized trials have demonstrated higher rates of LR following IORT compared to WBI.
Advantages:
improved patient convenience,
less absolute cost,
less acute skin erythema due to rapid dose falloff.
Disadvantages:
Lack of long-term efficacy data,
no pathology information available at the time of treatment,
inability to visualize dose to normal structures,
longer anesthesia time, and limited availability.
Dose falloff with 50 kV x-rays may be too steep, as evidenced by the increased risk of LR.
99
Partial breast irradiation rationale:
The rationale for APBI is that the majority of recurrences after BCT are seen at or near the tumor bed (~80%, compare this with the Holland study 40% tumours have foci >2cm away) and treating this region alone instead may eradicate residual disease while maintaining acceptable cosmesis and toxicity outcomes.
100
Advantages of PBI (Partial Breast Irradiation) include:
Shorter treatment time of ~5 to 15 days,
potentially less tumor repopulation between surgery and RT, and potentially better cosmesis (depending on technique).
101
Disadvantages of PBI include:
May miss multifocal disease - E.g. Holland study.
Cautionary criteria are debatable - e.g. inclusion of some invasive lobular disease.
102
What are the consensus guidelines for PBI?
What groups does it define?
What features are contraindications?
ASTRO consensus guidelines defines:
Suitable, Unsuitable, Cautionary.
Unsuitable group:
Age less than 50 with any cautionary or unsuitable path features.
Unsuitable features:
Node positive more than pNmi (pNmi is cautionary)
Margin positive
Clinically multifocal
Tumour ≥30 mm
103
Who may be suited to PBI (Partial Breast Irradiation):
The “suitable” criteria:
Age >50 yrs
1) Ductal:
Margins ≥2 mm
T1 (<=20mm)
pN0
Any grade
2) DCIS
Screen-detected
Low-intermediate grade
Tumour size ≤2.5 cm
Clear margins ≥3 mm
104
Who may be considered with caution for PBI?
40-49 years with only suitable pathology features
50-59 years with one of more cautionary pathology features
Suitable path features:
1) Ductal:
Margins ≥2 mm
T1 (<=20mm)
pN0
2) DCIS
Screen-detected
Low-intermediate grade
Tumour size ≤2.5 cm
Clear margins ≥3 mm
105
What age group can be considered for PBI despite cautionary path features?
50-59 years with one of more cautionary pathology features:
Lobular
21-30 mm
Limited LVSI
ER -ve
EIC <=3cm
106
Evidence for Partial Breast Irradiation
Numerous (>7) RCTs show that PBI is non-inferior or equivalent to WBRT.
In particular Import Low and the Florence study suggest w/IMRT doses of 40/15 or 30Gy/5 respectively equivalent outcomes, with improved acute and late toxicities, in particular cosmesis.
As an aside in UK consensus supports 26/5 partial breast dose.
107
A post menopausal 50yr woman has the following findings:
5.01cm grd II IDC, and four clinically +ve axillary nodes - one fixed.
What is the general diagnosis (what is the worst kind?) and approach?
Locally advanced breast cancer = characterized by advanced tumor (T3 or T4) or nodal stage (N2 or N3), generally including clinical stage IIB (T3N0) to stage III. This includes inflammatory breast cancer.
Patients are generally treated with neoadjuvant CHT, followed by surgery and adjuvant RT and endocrine therapy.
108
Evidence for Partial breast re-irradiation
There is no phase III data for this.
NRG Oncology/RTOG 1014 phase II trial: PBI following recurrence in the ipsilateral breast after previous WBI. Used BiD 1.5Gy for 15 days = 45/30 Bid. Suggest acceptable toxicity - (7%) had grade 3 and none had grade 4 or higher late treatment adverse events.
5-year cumulative recurrence incidence of 5%
109
DCIS represents ~X% of all BrCancers. Without tx, Z% to Y% can progress to invasive BC over T years.
Standard Tx involves?
After lumpectomy, adjuvant RT results in a relative RR in LR of?
(with approximately half of recurrences being invasive cancers) but no improvement in ?
Ductal carcinoma in situ (also known as intraductal carcinoma) represents ~20% of all BCs.
Without tx, up to 25% to 30% of DCIS cases can progress to invasive BC over 30 years.
Standard treatment involves either breast conservation therapy (lumpectomy plus adjuvant RT) or mastectomy.
After lumpectomy, adjuvant RT results in 50% relative RR in LR (with approximately half of recurrences being invasive cancers) but no improvement in overall survival.
Absolute risk of ipsilateral recurrence depends on grade, histologic subtype, size, ER status, and margin status.
110
LCIS is not detectable using which modality?
A distinctly different entity to LCIS - Mammographically undetectable
111
Histologic features of DCIS:
Histologic subtypes:
Which subtypes have worse prognosis?
DCIS implies that the basement membrane is preserved despite carcinoma in situ cells arising from the ductal epithelium. Typically grows toward nipple.
Nuclear pleomorphism, mitotic rate and cell morphology determine grade: I,II or III
Encompasses a heterogeneous groupin terms of histomorphology, underlying geneticss, biomarkers and potential for progression.
Five histologic subtypes (mnemonic: C2PMS):
cribriform, comedo (worst prognosis), papillary, micropapillary, solid (second worst prog).
prognosis).
112
DCIS histo grading is based on?
The likliehood of what other features increases with grade?
Nuclear pleomorphism, mitotic rate and cell morphology determine grade: I,II or III
Grd III - Typically exhibit aneuploidy, ER- and PR-negative and have a high proliferative rate, overexpression HER2, mutations of the p53 tumor suppressor, and angiogenesis in the surrounding stroma.
113
Histologic features of lobular carcinoma in situ (LCIS)
Noninvasive, neoplastic proliferation of small, uniform, dyscohesive cells, which originates in the terminal duct lobular unit (TDLU) and fills and distends most of the acini of the involved lobule.
Hallmark feature is loss of cellular cohesion due to dysfunctional E-cadherin catenin axis
114
Histologic features of Invasive lobular carcinoma
Invasive breast carcinoma with loss of cellular adhesion, characteristically arranged in discohesive single cells or single file patterns ("Indian filling").
Loss of E-cadherin expression on immunohistochemistry helpful but not required for diagnosis.
115
Indications to treat IMC
The evidence is not yet well defined, but should be considered in medial tumours w/ N2 or higher disease.
116
In cN0 disease but with positive nodes on SLNB, ALND is...?
Exceptions?
In cN0 disease but w/+ve nodes on SLNB, ALND is not recommended if pts will receive axillary radiotherapy and systemic therapy = Z0011 and AMAROS. In addition to providing no benefit in survival or recurrence rates, ALND resulted in worse lymphedema and paresthesia.
Z0011 and AMAROS should not be extrapolated to pts treated w/PBI or prone techniques, where less of the axilla would be treated
117
Prognostic and predictive factors for local recurrence and distant relapse after treatment of DCIS?
Prognostic:
Younger age (<50)
high grade,
comedonecrosis,
multifocality,
large tumor size,
positive surgical margins,
ER-negativity, HER2/neu amplification.
118
Name a prognostic scoring system for DCIS? What is it comprised of?
What is its limitation?
Van Nuys Prognostic Index (VPNI) - low score 4–6, intermediate, and
high 10–12.
Based on 4 things:
Age <40 = 3, >60 = 1
Size
Margins - less than 1mm is 3
Grade
Has only been retrospectively validated
119
General treatment paradigm for DCIS:
Options include observation if short life expectancy due to comorbidities,lumpectomy alone, lumpectomy with adjuvant RT ± tamoxifen/anastrozole (based on menopausal status and if ER-positive) or mastectomy.
A risk-based patient-specific assessment is necessary.
Oncotype Dx studies suggest DCIS has same range of gene changes as IDC and is therefore a heterogenous grouping in which some low risk pts may not benefit from RT.
120
Would you recommend hormone therapy for DCIS?
NCCN recommends tamoxifen for patients
with ER-positive tumors treated with excision alone or lumpectomy and RT.
E.g. with hormone therapy the recent TROG DCIS boost study suggests a NNT around 24 for a benefit to boost.
121
Benefit of XRT post lumpectomy for DCIS:
At least 5 RCTs support a LC benefit (including one supporting boost) for adJXRT. These are further supported by meta-analysis. There is no OS or cancer specific survival benefit.
Meta-analysis: RT reduced 10-year risk ofipsi breast recurrence relative risk by 54% and 15% absolute RR (NNT 6.7), with a greater proportional reduction in older women.
122
Is adjuvant tamoxifen beneficial in DCIS? Who should receive it? What is the optimal dose?
For ER +ve patients:
Tamoxifen lowers the incidence of any breast event (B24 and UK/ANZ) and contralateral breast events BUT does not affect ipsilateral invasive recurrences and therefore is not a substitute for RT (UK/ANZ).
Tamoxifen benefits only ER-positive patients (B-24).
123
The impact of margins of resection on the risk of local recurrence:
Recent large-scale meta-analysis (published BMJ) links margin status to
local and distant recurrence AND overall survival (effect persit despite CTx and RT):
Positive or close inked margin: increased risk local and distant spread decreased OS
<1mm:
increased risk local and distant spread
124
Pathological findings for inflammatory breast cancer:
Clinicopathologic Dx: characterized by rapid onset (≤ 6 months) and enlarged, erythematous and edematous (peau d’orange) breast due to dermal plugging of lymphatic vessels by tumor.
Involved dermal lymphatics alone, wo classic clinical presentation is not = inflammatory carcinoma
125
Technique to Dx inflammatory breast cancer (assuming clinical criteria met)
Clinical features: Rapid onset (≤ 6 months) and enlarged, erythematous and edematous (peau d’orange).
At least 2 skin punch biopsies between 2 - 8 mm of the most prominent area of skin discoloration.
Histo:
Tumor microemboli in the lymphatic spaces causes obstruction that leads to the clinical presentation of peau d’orange appearance.
RhoC overexpression induces angiogenesis and facilitates rapid metastasis.
E-cadherin accumulation/ overexpression within tumor emboli
Imaging: May or may not have a breast mass, mammogram not vey useful.
126
In the setting of locally advanced breast cancer, what is the benefit of adjXRT post mastectomy?
At least three randomized trials from the 1990s have demonstrated a survival benefit to post-mastectomy RT for high-risk patients, particularly those with LN+ disease.
BUT: In the modern era, the risk of LRR in pT1–2N1 patients without PMRT is less (<10%) compared to historical series (20%–30%), and so this remains a controversial subgroup.
More recent analysis in B-27 suggests 10-year risk of LRR is significant after neoAdjCTx (>10%) for the following patients:
tumor size >5 cm, positive axillary lymph nodes, younger age, and incomplete response to NACT
portend a higher risk of LRR.
127
Recent evidence suggests which subgroups of locally advanced patients benefit from XRT post mastectomy and chemo?
More recent analysis in B-27 suggests 10-year risk of LRR is significant after neoAdjCTx (>10%) for the following patients:
tumor size >5 cm,
positive axillary lymph nodes,
younger age, and
incomplete response to NACT
portend a higher risk of LRR.
Meta-Analysis of Gepar Trials (Ann Surg Oncol 2019):
RT reduces LRR rates in breast cancer patients who undergo mastectomy after NACT, including high-risk patients with pCR to NACT.
128
In the setting of mastectomy and systemic therapy, are T3N0 tumors at high risk for recurrence? And is there a role for radiation?
What is the local failure rate for mastectomy and chemo alone?
Differentiate 2 potential subgroups of T3N0 patients
The utility of post-mastectomy RT (PMRT) for pT3N0 patients is controversial.
At least two large RRs show low LF rates <10% for mastectomy + systemic therapy alone for pT3N0.
Conversely, a 2014 SEER analysis and single-institution
data suggest a benefit w/PMRT for pT3N0 patients.
Notably, cT3N0 are often under-staged in terms of nodal involvement, and thus have a different prognosis than pT3N0.
129
Recent evidence suggests which subgroups of locally advanced patients benefit from XRT post mastectomy and chemo?
More recent analysis in B-27 suggests 10-year risk of LRR is significant after neoAdjCTx (>10%) for the following patients:
tumor size >5 cm,
positive axillary lymph nodes,
younger age, and
incomplete response to NACT
portend a higher risk of LRR.
