Percorso di cura e trattamento
riabilitativo della paziente operata
di tumore alla mammella
La chirurgia oncoplastica
della mammella
Il moderno approccio alla
chirurgia ascellare
Venere e Cupido, Moreelse Paulus, 1617, Hermitage - St.Petersburg
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1
Oncoplastic Breast Surgery
“Così come si provocano o si esagerano i dolori dando loro importanza, nello stesso modo questi
scompaiono quando se ne distoglie l'attenzione.”
Sigmund Freud
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1894
massimo
trattamento
tollerabile
TRIAL MILANO I (1981)
(T1 N0 : QUART VS HALSTED)
1981
minimo
trattamento
efficace
In pratica…
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1894  1981 = 87 anni
Mastectomia “radicale” di Halsted, mastectomie modificate
sec. Patey e Madden con linfadenectomia ascellare
1981  1998 = 24 anni
Quadrantectomia + radioterapia + linfadenectomia 
Quadrantectomia + radioterapia + biopsia linf sentinella
1998  oggi
Chirurgia Oncoplastica + radioterapia + biopsia
linfonodo sentinella
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Definizione di Chirurgia Oncoplastica
Consensus Conference Firenze 1998
Il termine di chirurgia oncoplastica comprende in sé il doppio significato di
resezione oncologica, finalizzata al controllo locale della malattia, e di
ricostruzione plastica per ottenere il migliore risultato cosmetico possibile.
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Il chirurgo senologo oncoplastico
Punti chiave
Criticità
Volume tumore/Volume mammella
Curva di apprendimento
(tecnica e culturale)
Forma della mammella
Localizzazione del tumore
Caratteristiche del tumore
Terapie adiuvanti (RT, CT, HORMT)
Complicanze postoperatorie (liponecrosi
5%)
Tempo di sala operatoria
(maggiori risorse)
Corretta informazione alla paziente
Desideri della paziente
Gruppo di Specialisti
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Interventi chirurgici personalizzati
Casi clinici personali
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Chirurgia oncoplastica della mammella
Removing a portion higher than 20% of the whole breast volume is a predictive factor of poor
aesthetic outcome
European Breast Cancer Conference (Vienna 2012): Oncoplastic Techniques
VOLUME
DISPLACEMENT
1st level: reshaping with glandular flaps with/without contralateral carried out
by oncoplastic breast surgeon
2nd level: glandular reshaping by means of upper, mid, lower and lateral
peduncle flaps, performed by the oncoplastic breast surgeon and
without the support of the plastic surgeon
3rd level: “conservative mastectomies” (nipple sparing, skin sparing, skin
reducing) and reconstruction with expandable implants, performed
jointly by the breast and plastic surgeons
VOLUME
REPLACEMENT
4th level: complex mammary reconstruction with muscle and skin flaps that
require the exclusive presence of the plastic surgeon
Margini
> 3 cm
16%
2 cm
40%
≤ 1 cm
57%
For successful results surgeons and patients should discuss their options before surgery
and the surgeon should ideally be proficient in various oncoplastic techniques
The surgical margin status has been accepted to be the most
important risk factor, because it is the only risk factor which is
controllable by surgeon.
surgeon
There is no clear consensus as to the definition of a positive surgical
margin.
margin
It might be reasonable for positive surgical margins to include atypical
cells, in situ or invasive cancer cells within 5 mm from cut surface
Oncoplastic surgery, such as the use of a partial flap and the insertion of a prosthesis,
could be an option for obtaining both a clear resection margin and a better cosmetic
result
What is a negative margin?
for Radiation Oncologists in North America
No malignant cells seen on the inked surface
No malignant cells seen at: 1 mm
2 mm
3 mm
5 mm
10 mm
for Radiation Oncologists in Europe
15%
21%
50%
12%
10%
3%
No malignant cells seen at > 5 mm
Meta-analysis by Wang et al. > 10 mm
Meta-analysis by Houssami et al.  No statistical difference in local recurrence
associated with margin widths of more than 1 mm, more than 2 mm, or more than 5mm
after adjustment for a radiation boost and endocrine therapy
Recidiva locale dopo chirurgia oncoplastica
Fattori di rischio della recidiva locale
Grado 3
RR 2,5
Ca lobulare invasivo
RR 2,5
Margini positivi
RR 2,4
Invasione linfovascolare
RR 1,8
pT > 2cm
RR 1,5
Linfonodi positivi
RR 1,4
Età < 40 anni
RR 1,4
Canada, NSABP B-06, Milano 2 e 3 Trials
Preoperative breast MRI imaging
Preoperative breast MRI changed the surgical plan to more extensive surgery in 34% of cases.
tumor positive resection margins
control group
15.8%
29.3%
(p < 0.01)
Impact on surgical management attributed to MRI findings
conversion to mastectomy
conversion to wider excision
conversion from wide local excision to mastectomy
8.3%
4.5%
8.1%
Lancet 2005
La recidiva locale assume un significato prognostico
Confermato anche nella revisione del 2011
Neoplasia del quadrante supero esterno
Reshaping ghiandolare di 1° livello con centralizzazione del NAC
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Neoplasia del quadrante supero esterno
Reshaping ghiandolare di 1° livello
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Neoplasia della confluenza dei quadranti inferiori
Reshaping ghiandolare di 2° livello: lembo a peduncolo superiore
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Neoplasia della confluenza dei quadranti superiori
Reshaping ghiandolare di 2° livello: lembo a peduncolo inferiore
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Le mastectomie conservative sec. Nava
Chirurgia Oncoplastica di 3° livello
SKIN REDUCING MASTECTOMY SEC.NAVA
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Le mastectomie conservative sec. Nava
Chirurgia Oncoplastica di 3° livello
SKIN SPARING MASTECTOMY
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Le mastectomie conservative sec. Nava
Chirurgia Oncoplastica di 3° livello
NIPPLE SPARING MASTECTOMY
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Oncoplastica
Impiego della cellulosa ossidata rigenerata
Indicazioni
- Filler in qualunque settore ghiandolare
- Parenchima mammario con scarso contenuto adiposo
- Mammella piccola
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Il confort della paziente:
la gestione della ferita chirurgica e il miglior risultato cosmetico possibile
Dal 13 al 35% dei pazienti
medicati con cerotti convenzionali
sviluppano
delle
vescicole
dolorose capaci di ritardare la
guarigione
della
ferita
e
aumentare il rischio di infezioni del
sito chirurgico
Ousey K. et al. Understanding and preventing
wound blistering. Wound UK, 2011.
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Mepilex® Border Post-Op
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2
Il
Development of
axillary surgery in breast cancer
tocco
supremo
dell'artista:
sapere
quando
fermarsi
ARTHUR CONAN DOYLE "L'avventura del costruttore di Norwood
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Razionale storico della dissezione ascellare
1. Migliore controllo locale della malattia
2. Prevenzione delle recidive ascellari
3. Miglioramento della sopravvivenza nei casi di macrometastasi
4. Completamento della stadiazione con indicazione alla chemio/radioterapia *
Timeline of the axillary surgery
Axillary Dissection
18th
century
Heister:
axillary
dissection
as part of
the
treatment
of invasive
breast
cancer
1875
Volkman
observed the
communicati
on of the
mammary
lymphatic
vessels with
the axillary
nodes
1867
Moore
proposed
the complete
removal of
the breast
and the
”diseased
glands”
1882
Banks and
Moore:
“the axillary
nodes should
be removed
even when
they
were not
clinically
involved”
1891
William
Halsted
described the
theory
of
centrifugal
spread of
breast cancer
SNB
1948
Patey and
Dyson
less radical
approach:
the
pectoralis
major
was
preserved
1970
1992
1993
Veronesi
National
Krag,
QUA-Rt
Cancer
SNB for
achieved the
Institute
breast
same results
Bethesda
cancer
of radical
mastectomy +
ALND as
integral
Morton DL, Wen DR, Wong JH et al
part of the
(1992)
Technical
details
of
procedure
intraoperative lymphatic mapping for
early stage melanoma. Arch Surg
127:392–399
Linfonodo sentinella
Accuratezza diagnostica 96.5% - Valore predittivo negativo 94-96% - Falsi negativi ~ 5%
La probabilità di trovare un sentinella positivo nelle pazienti clinicamente negative è del
20-30%
LINFONODO SENTINELLA POSITIVO PER CELLULE
TUMORALI ISOLATE
(cluster di cellule con Ø massimo < 0,2 mm)
mm
LINFONODO SENTINELLA POSITIVO PER
MICROMETASTASI (0,2 mm < Ø < 2 mm)
mm
screening
LINFONODO SENTINELLA POSITIVO PER
MACROMETASTASI (Ø > 2 mm)
mm
Dutch MIRROR retrospective study
(chemo, hormonal,both)
Disease
Free
Survival
A
pN0
-
85.7%
B
pN0[i+] /
pN1mi
-
76.5%
< 0.001
C
pN0[i+] /
pN1mi
+
86.2%
< 0.001
5-year
Adiuvant
therapy
p
Isolated tumor cells or micrometastases in regional lymph nodes were associated with a reduced 5-year
rate of disease-free survival among women with favorable early-stage breast cancer who did not receive
adjuvant therapy. In patients with isolated tumor cells or micrometastases who received adjuvant therapy,
disease-free survival was improved
the incidence of nonsentinel
node metastases increased as
the primary tumor increased in
size and more important the size
of sentinel node metastases.
T1 lesions
(< 2 cm)
nonSN MTS
SN microMTS
6%
(0,2 – 2 mm)
SN macroMTS
47,5%
( > 2 mm)
Axillary Dissection is still usefull? Yes..
Axillary lymph node dissection (ALND) has remained standard treatment for women
with node-positive disease detected clinically and/or confirmed pathologically,
irrespective of the primary tumour characteristics. Removal of axillary nodes containing
tumour foci provides regional control and may remove a potential source of distant
metastases
…but
Even after ALND of level I and II, up to 30% of positive lymph nodes remain in the axilla
…but
Extended surgery is considered to be less influential on overall survival in patients
with breast cancer than systemic therapy and radiotherapy
…in fact with adjuvant therapy and radiotherapy
How to study axillary lymph nodes ?
actual indications
Guidelines and Clinical Recommendations
Dott. PC Rassu,
2013
Axillary staging
Surgical Staging
Sentinel Lymph Node Biopsy
Axillary Lymph Node Dissection
Instrumental +
Surgical Staging
Instrumental Staging
Clinical examination
US + FNAC/CB
Digital Mammography
Computed Tomographyc Scan
Positron Emission Tomography
Magnetic Resonance Imaging
Physical examination
Clinical examination is the oldest and most rudimentary method used to evaluate lymph
node status and manifestly inaccurate for axillary staging: the physician cannot
differentiate between an enlarged lymph node that is cancerous versus one that is
inflamed or reactive. Among patients with non-palpable nodes in the axilla, the
histopathological presence of metastasis was found in 35–40%
Lanng showed in a study involving 301 patients that even if the examination was
performed by a specialist breast surgeon, the examination had little value. When the
surgeons considered the axilla to be normal, they were wrong in 44% of cases.
cases
sensitivity: 25–32%
US examination
Metastases develop preferentially in the LN cortex
sensitivity: 45–86%
Rounded shape, a long-to-short axis ratio of 2, hypoechoic, compression or
disappearance of the fatty hilum, cortical thickening or asymmetry
If a suspicious lymph node is found on imaging, patients may undergo US-guided fineneedle aspiration or core needle biopsy to obtain a cytologic or histologic diagnosis
MR examination
sensitivity: 37%
lesions ≤ 2 mm may
not be visualized
directly
FDG-PET examination
FDG-PET is not yet sufficiently sensitive in the detection of lymph node metastases; the
modest results of PET in the detection of micrometastases are likely due to the limited
spatial resolution of the current PET scanners
Spatial resolution of PET scanner:
-adequate (sensitivity 100%) for metastases ≥10 mm in diameter
-acceptable (sensitivity 83%) for metastases between 6 and 9 mm
-inadequate (sensitivity 23%) for metastases <5 mm
sensitivity: 23–100%
La biopsia del linfonodo sentinella è da considerare lo standard per le pazienti con
linfonodi ascellari clinicamente negativi o con linfonodi clinicamente sospetti ma con
successivo agoaspirato negativo.
(raccomandazione tipo A, livello di evidenza I)
SNB vs AD
SNB neg
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial revealed no significant
differences in overall survival, disease-free survival or regional control
SNB pos
In presenza di micrometastasi nel linfonodo sentinella, la successiva effettuazione della
dissezione ascellare oppure la non effettuazione della dissezione ascellare danno gli
stessi risultati in termini di sopravvivenza libera da malattia a 5 anni e di sopravvivenza
globale
Isolated tumor cells and micrometastases in a single sentinel node, were not considered
to constitute an indication for axillary dissection regardless of the type of breast surgery
carried out.
The Panel accepted the option of omitting axillary dissection for macrometastases in the
context of lumpectomy and radiation therapy for patients with clinically nodenegative
disease and 1–2 positive sentinel lymph nodes as reported from ACOSOG trial Z0011
with a median follow-up of 6.3 years.
The Panel, however, was very clear that this practice, based on a specific clinical trial
setting, should not be extended more generally,
generally such as to patients undergoing
mastectomy, those who will not receive whole-breast tangential field radiation therapy,
those with involvement of more than two sentinel nodes, and patients receiving
neoadjuvant therapy
5-year
SLND
ALND
overall survival
92.5% (95% CI,
90.0%-95.1%)
91.8% (95% CI,
89.1%-94.5%)
disease-free
survival
83.9% (95% CI,
80.2%-87.9%)
82.2% (95% CI,
78.3%-86.3%)
local recurrence
1.6% (95% CI,
0.7%-3.3%)*
3.1% (95% CI,
1.7%-5.2%)
* pz sottoposte a radioterapia e tp adiuvante
Criticità dello studio
Reclutamento stimato 1900 pz, reale < 891 (47% del totale, con riduzione della potenza statistica)
Interruzione precoce dello studio per mancanza di effetti avversi, ovvero per avere il tasso di morti stimato
(Hazard Ratio 1,3) ci sarebbero voluti fino a 20 anni di follow up
Perdita delle pazienti al follow up > 17%, per mantenere una sufficiente potenza statistica le perdite al follow up
devono essere < 10 %
Quasi tutte le pazienti dello studio hanno eseguito terapia adiuvante (chemio 58%, ormono 46%) e radioTP whole
breast (89%)
Non sono stati chiariti i criteri di selezione per pazienti HER2+ e triple negative
IBCSG Trial 23-01 di NON inferiorità
6681 casi eleggibili di cui solo 931 randomizzati
Per avere una potenza statistica sufficiente l’accrual doveva comprendere almeno 1960 pazienti (aprile 2001,
febbraio 2010). Per aumentare l’accrual nel 2006 sono stati arruolati anche i casi multicentrici e multifocali
(sebbene formalmente dovevano essere sono unicentrici) e neoplasie con diametro ≤ a 5 cm (sebbene
formalmente dovevano essere ≤ a 3 cm)
I 931 casi randomizzati (464/467) avevano neoplasie ER/PgR +, G1-G3, con istotipo duttale e lobulare, SN+
(microMTS e ITC, ma non con macroMTS).
macroMTS Le ITC sono state paragonate alle microMTS (!).
Endopoint: Disease Free Survival, Overall Survival, Axillary recurrences
Follow up 60 mesi
Esclusioni: neoplasie HER2 + e triplo negative; DCIS puro, chemioTP neo-adiuvante, malattia metastatica,
ascella clinicamente impegnata, malattia di Paget senza neoplasia invasiva, donne in gravidanza o in
allattamento.
DFS a 5 anni: DLA/non DLA 88%
OS a 5 anni: DLA/non DLA 98%
Discussione multidisciplinare
Tumor biology in axillary management
Gene expression patterns classifies breast cancer into major subtypes:
Luminal like
A  ER/PgR (+), HER2 (-), Ki67 < 14%
B1  ER/PgR (+), HER2 (-), Ki67 > 14%
B2  ER/PgR (+), HER2 (+)
HER2-enriched  ER/PgR (-), HER2 (+)
Basal like, triple negative  ER/PgR (-), HER2 (-)
Breast cancer is not a single disease with variable morphological features, but rather a
group of molecularly distinct neoplastic disorders, the intrinsic biological behavior of
which may influence natural history and, consequently, clinical management
OncotypeDX® measures the expression of 21 genes.
genes
By combining the expression levels of these genes, a quantitative
recurrence score (RS) is calculated.
OncotypeDX® was able to stratify patients into low-, intermediate- and
high-risk categories
Mammaprint® measures the expression of 70 genes.
It calculates a prognostic score that categorizes patients under good
and poor risk groups
QUANDO È INDICATA LA DISSEZIONE ASCELLARE ALLA LUCE DEI DATI E
DELLE LINEE GUIDA ATTUALMENTE PUBBLICATE (FIM 23 gennaio 2013)
La dissezione ascellare in caso di linfonodo sentinella positivo per micrometastasi può
essere omessa quando la paziente soddisfa i seguenti criteri:
Ecografia ascellare preoperatoria: negativa
FNAC/CB di linfonodi sospetti ascellari: negative
Chirurgia mammaria conservativa con successiva
- radioterapia whole breast
- chemioterapia adiuvante
- ormonoterapia adiuvante
La discussione multidisciplinare così come un adeguato consenso informato della
paziente sono fondamentali in tutti i casi, ma soprattutto in quelli con neoplasie
biologicamente più aggressive.
www.fimcasiclinici.it
Presidio ospedialiero di NOVI LIGURE
Ospedale SAN GIACOMO
Ambulatorio di
SENOLOGIA CHIRURGICA
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