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« Israeli-French Breast Cancer Update »
Prevention, Detection and Treatment,
Multidisciplinary approach
Dr Jean-Yves SEROR (Paris, France)
Small lesions ≤ 1 cm.
Imaging features.
T1a > 1mm and < 5mm T1b > 5 mm and < 10mm
T1c > 10mm et < 20 mm
Global survival at 5 years vs size
S < 20 mm 91 %
20 < S < 50 mm 80 %
S > 50 mm 60 %
Definition TNM T1a and T1b (T1< 20 mm)
Cancello & al, Br Can res and TTT 2011
N+
N-
T < 10 mm
Recurrence at 10 years <10%
• Tumors most frequently not palpable, detected through screening
• Infra-centimetric = Not palpable
• HER2 +
• Triple Negative
• Young old patientGood prognosis
Biological
Heterogenicity
In France , the infra centimetric breast cancers
represent today 25 to 30 % of these newly diagnosed
cancers.
37 % of the invasive cancers diagnosed within this
screening campaign have a size ≤ 10mm
France : National Breast Cancer Screening
Tumor size : The largest diameter of the bigger tumoral
nodule present
Definitions
In case of difference between the macroscopic and microscopic measure, the
microscopic measure of the invasive contingent should be taken into account
for the grading
Lobular Invasive carcinoma: underestimation of the size
7 mm
• When measuring, do not take into account
the in situ adjacent carcinomas
• In case of multiple tumor, do not sum sizes
Uni focal
infra-centimetric
tumor
infra-centimetric tumor
+ DCIS (microcalcifications)
TOMOSYNTESIS
Not taking into account in the measurement , the
DCIS adjacent
Infra-centrimetric tumor : UNIFOCAL
In case of multiple tumor
• Do not sum the sizes for the TNM
• Total size : surgical management
Infra centimetric tumors : MULTIFOCAL
Tumoral distribution
Regarding small size tumors (≤ 9 mm), vascular embolus and nodes extension
are most frequent for multifocal tumors 1
71. Tot T, Pekár G, Hofmeyer S, et al. The distribution of lesions in 1-14-mm invasive breast carcinomas and its relation to metastatic potential. Virchows Arch.
2009 Aug;455(2):109-15.
137 tumors between 1 & 9 mm (55 %)
Unifocal tumors Multifocal tumors
Invasive carcinoma 1-9 mm 97 71 % 40 29 %
Vascular embolus 9 9 % 14 35 %
RR = 3.8144
95 % CI = 1.7960-8.0870
Ganglionic extension 5 5 % 5 13 %
RR = 2.4250
95 % CI = 1.7424-7.9266
Infra centimetric tumors and mammography
Infra centimetric tumors and ultrasound
Infra centimetric tumors and MRI
Imaging specificities for lesions < 1 cm
9
Infra centimetric tumors
and mammography
Compared to tumors > 2 cm, detection of infra centrimetric tumors not
seen on mammography but only under ultrasound 1: x 2,2
1. Bae MS, Han W, Koo HR et al. Characteristics of breast cancers detected by ultrasound screening in women with negative mammograms.
Cancer Sci. 2011 Oct;102(10):1862-7.
Se 80% [78-82%]
Density 1 98%
Density 2 83%
Density 3 64%
Density 4 48%
2. DEMIST Digital Mammographic ImagingScreeningTrial ) Pisano ED et al. New Engl. J. Med 2005
The mammography sensitivity is related to the breast density
• The higher the breast density, the lower the detection sensitivity1
• Variation of 64 % for breasts with a very high density to 87 % for very fatty
breasts 2
7 mm
Infra centimetric tumors and mammography
16 %
43 %
21 %
43 %
Isolated microcalcifications cluster ( 43% ) Indicating an in situ lesion
Rounded ( 20 %) or spiculated opacity (21%)
Opacity and microcalcifications ( 16 % )
Inv Carcinoma
Radial scar
With mammography small cancers can be seen :
microcalcifications
Bi-Rads 3 BIRADS 4 ?
• Analysis and detection of microcalcifications clusters on X-ray images
Magnification views +++
• BIRADS : THE MORPHOLOGY is the first semiologic element to be taken into
account before the evolvement
Diagnostic pitfall
13 months
DCIS comédo
1. Berg WA et al Cystic breast masses and the acrin 6666 experience. Radiol Clin North Am 2010;48:931-87
• These small rounded tumors should not be
wrongly interpreted as intra-mammary
lymph nodes.
• You should be careful with stable lesions
compared with the last medical balance and
with lesions not found again under
ultrasound.
• Women with Family history ++ Misleading
aspect of some lesions : rounded, regular,
pseudo cystic image.
With mammography small cancers can be seen (follow) :
Round tumor with benign appearance 1
Diagnostic pitfall
P David, J Le Sein Septembre 2004)
Relation between size and tumoral growth
Misleading rounded shapes
Irregular outlines
Bi-Rads 3 : if follow up ….
 Opacity control at 4 months
 Microcalcifications at 6 months
• Growth speed
• Intensity of the surrounding tissue reaction
2009
2009
Bi-Rads 2 ? Bi-Rads 3 ?
Eric L Rosen and al Malignant Lesions Initially Subjected to Short-term Mammographic Follow-up Radiology 2002;223:221-228
2011 2011
Rosen: 4/12 opacities classified as node
3. Burrell HC, Sibbering DM, Wilson AR et al. Screening interval breastcancer : mammographic features and pronostic factors. Radiology
1996;199:811-7.
4. Andersson I, Ikeda DM, Zackrisson S et al. Breast tomosynthesis and digital mammography: a comparison of breast cancer visibility and
BIRADS classification in a population of cancers with subtle mammographic findings. Eur Radiol. 2008 Dec;18(12):2817-25.
15
• Variation of the aspect according to the
incidence or visibility under a sole incidence
• The most frequent cause of interval cancers 3
• The breast tomosynthesis by reducing the
tumor and gland superposition effects ,
should improve the sensibility versus the
mammography 4
With mammography small cancers can be seen as :
architectural distortion
Diagnostic pitfall
2010 2012
Invasive carcinome
4 radiologists
12631 women
Cancer n = 121
Mammo 2D Mammo 2D
+
Mammo 3D
2 incidences
Delta p
False positives 6,1% 5,3% 15% P < 0,001
Cancers detection
121 soit 9,5 %o
77/121
6,1%o
101/121
8%o
24
27%
P < 0,001
Invasive cancers detection
56
4,4%o
81
6,4%o
25
40%
P < 0,001
Oslo trial Nov 2010 – Dec 2011 25 000 women
Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-
based screening program.
Skaane P et Al. Radiology. 2013 Apr;267(1):47-56.
BIRADS 0 ?
Doubt in mammography with an abnormality not accessible for a
biopsy under ultrasound or stereotaxy
Doubt
in mammography
ACR 4
Negative Predictive Value :
Normal MRI allows to clear these images
In front of a small tumor detected under ultrasound, the signs with
the highest cancer positive predictive value are :
The irregular shape : 62 %
The orientation not parallel to the skin : 69 %
The spiculated margins : 86 %
1 sign only : eliminate the benignancy
Ultrasound signs : T1b > T1a
Infra centimetric tumors and ultrasound
The diagnostic value of the ultrasound is superior if the echography is guided by an
abnormality detected on the mammography vs screening ultrasound
1. Iso-echogenic lesions (10 % of cancers)
2. Some high grade small cancers
Posterior reinforcement of the ultrasonic beam due to their high
cellularity
Regular margins due to their fast growth
Histology : Papillary carcinoma
Infra-centimetric tumors and ultrasound
Diagnostic Pitfall
1 2 3
Cysts , fibroadenoma and carcinoma ?
Medularry Carcinoma
Size 10 mm RH- Her2 +
Post puncture
Masses Enhancement
(visible tumor in 3 planes > 5mm)
Non mass Enhancement Foci each enchancement < 5mm
Enhancing lesions
Sensibility1,2
95-100 % in infiltrative Carcinoma
70-75 % in Ductal carcinoma In situ (DCIS)
1 Liberman L, Morris EA, Joo-Young Lee M et al. AJR Breast lesions detected on MR Imaging: features and positive predictive value. AJR 2002;179:171-178
2 Schelfout K, Van Goethem M, Kersschot E, et al. Preoperative breast MRI in patients with invasive lobular breast cancer. Eur. Radiol 2004;14:1209–1216.
3 Fabre Demard N, Boulet P, Prat X et al. Breast MRI in invasive lobular carcinoma: diagnosis and staging].J Radiol 2005;86(Pt 1):1027–1034.
Infra centimetric tumors and RMI
73% Invasive carcinoma
• DCIS
• Invasive lobular carcinoma 3
Focal adenosis,Invasive carcinoma,
DCIS, papilloma, fibroadenoma, LN…
False negatives: the causes
Weak tumoral angiogenesis and therefore low enhancement :
• Histological type (5 % of the RMI FN)
 Ductal Carcinoma In situ (DCIS)
 Medularry Carcinoma Breast
 Some Invasive Lobular Carcinoma (ILC) or with a consequent fibrous contingent
• Small size cancers (Up to 3 % of false negative)
Infra centimetric tumors and RMI
Diagnostic Pitfall
Enhancement
 Absent (few or no angiogenesis)
 Not seen (masked effect)
 Wrong interpretation (Focus)
Be careful with the mammary gland PHYSIOLOGICAL ENHANCEMENT particularly during the 2nd part
of the menstruation ( RMI exam to be performed between the 7th and 13rd day of the menstruation)
Background Parenchymal Enhancement : risk of hiding a small lesion
minimal mild
moderate marked
Bi-Rads IRM 2013
28
• FOCI 1,2
CARACTERIZATION
 Punctiform enhancements < 5 mm
Not visible before injection +++ (T1 / T2)
Unique or multiple
• Up to 29 % of the patients presenting a suspicious lesion under mammography
or ultrasound
1. Kuhl CK, Kreft BP, Hauswirth A et al. [MR mammography at 0.5 tesla. II. The capacity to differentiate malignant and benign lesions in MR mammography at
0.5 and 1.5 T].] Rofo 1995 Jun;162(6):482-91.
2. Brown J, Smith RC, Lee CH. Incidental enhancing lesions found on MR imaging of the breast. AJR Am J Roentgenol. 2001 May;176(5):1249-54.
Infra centimetric breast carcinoma and RMI
Mass enhancement :
Invasive ductal Carcinoma
Foci : Non mass enhancement < 5mm
CCI SBR2 Re+ Rp- Her2 -
Right Breast ultrasound
45% echo-guided biopsy
55 % of the lesions not found
DeMartini et al. Utility of Targeted Sonography for Breast Lesions That Were Suspicious
on MRI. AJR 2009;192:1128
SECOND LOOK ULTRASOUND
VPP 96 % T > 20 MM
VPP 62% T < 20 MM
Microcalcifications
NME > 5 mm
Infra centimetric lesions : biopsies
Pre-operatory diagnosis
Difficult Extemporaneous
 Malignity
 Infiltrating ?
 Prognosis factors
 Grade
 HER2 +++
 Hormonal
status
 Lesions spreading
Limits and difficulties of infra-centimetric lesions echo-
guided microbiopsies ( T1a < 5 mm)
Small size lesions?
3 -4 mm ? Visibility
Post biopsy for small size
lesions
Pre-operatory localization
X-ray ultrasound correlation
X-ray of the operative element
After biopsy of small lesions
(< 5mm)
“The mean size of such image-detected carcinomas
is 11mm and 90% will be node negative.”
“Errors in determining tumor size result from
summing the sizes of the carcinoma
• In multiple separate morcellated fragments
of a resection
• Or in the multiple separate fragments of a
core biopsy procedure.”
Issues with Tumor Size Assessment
Michael Lagios, MD Seminars Breast Disease 2006, Volume 3, No. 9
T1a et T1b
20 mm
10mm
Conclusion
Small lesions ≤ 1 cm. Imaging Features.
• Tumors with a good prognosis but up to 20% are N+
• Clinical exam + imaging : early diagnosis
• Delayed diagnosis : Pitfall
 Histological
 Screening
 Misleading appearance
• Importance of a high quality imaging, knowing the limits.
• Pre-operative diagnosis +++
• In case of doubt, sampling rather than close control
Dr Jean-Yves SEROR (Paris, France)
« Israeli-French Breast Cancer Update »
Prevention, Detection and Treatment,
Multidisciplinary approach
Small lesions ≤ 1 cm.
Imaging features.

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Jean Yves Seror : Breast cancer : Small lesion imaging features

  • 1. « Israeli-French Breast Cancer Update » Prevention, Detection and Treatment, Multidisciplinary approach Dr Jean-Yves SEROR (Paris, France) Small lesions ≤ 1 cm. Imaging features.
  • 2. T1a > 1mm and < 5mm T1b > 5 mm and < 10mm T1c > 10mm et < 20 mm Global survival at 5 years vs size S < 20 mm 91 % 20 < S < 50 mm 80 % S > 50 mm 60 % Definition TNM T1a and T1b (T1< 20 mm) Cancello & al, Br Can res and TTT 2011 N+ N- T < 10 mm Recurrence at 10 years <10% • Tumors most frequently not palpable, detected through screening • Infra-centimetric = Not palpable • HER2 + • Triple Negative • Young old patientGood prognosis Biological Heterogenicity
  • 3. In France , the infra centimetric breast cancers represent today 25 to 30 % of these newly diagnosed cancers. 37 % of the invasive cancers diagnosed within this screening campaign have a size ≤ 10mm France : National Breast Cancer Screening
  • 4. Tumor size : The largest diameter of the bigger tumoral nodule present Definitions In case of difference between the macroscopic and microscopic measure, the microscopic measure of the invasive contingent should be taken into account for the grading Lobular Invasive carcinoma: underestimation of the size 7 mm • When measuring, do not take into account the in situ adjacent carcinomas • In case of multiple tumor, do not sum sizes
  • 5. Uni focal infra-centimetric tumor infra-centimetric tumor + DCIS (microcalcifications) TOMOSYNTESIS Not taking into account in the measurement , the DCIS adjacent Infra-centrimetric tumor : UNIFOCAL
  • 6. In case of multiple tumor • Do not sum the sizes for the TNM • Total size : surgical management Infra centimetric tumors : MULTIFOCAL
  • 7. Tumoral distribution Regarding small size tumors (≤ 9 mm), vascular embolus and nodes extension are most frequent for multifocal tumors 1 71. Tot T, Pekár G, Hofmeyer S, et al. The distribution of lesions in 1-14-mm invasive breast carcinomas and its relation to metastatic potential. Virchows Arch. 2009 Aug;455(2):109-15. 137 tumors between 1 & 9 mm (55 %) Unifocal tumors Multifocal tumors Invasive carcinoma 1-9 mm 97 71 % 40 29 % Vascular embolus 9 9 % 14 35 % RR = 3.8144 95 % CI = 1.7960-8.0870 Ganglionic extension 5 5 % 5 13 % RR = 2.4250 95 % CI = 1.7424-7.9266
  • 8. Infra centimetric tumors and mammography Infra centimetric tumors and ultrasound Infra centimetric tumors and MRI Imaging specificities for lesions < 1 cm
  • 9. 9 Infra centimetric tumors and mammography Compared to tumors > 2 cm, detection of infra centrimetric tumors not seen on mammography but only under ultrasound 1: x 2,2 1. Bae MS, Han W, Koo HR et al. Characteristics of breast cancers detected by ultrasound screening in women with negative mammograms. Cancer Sci. 2011 Oct;102(10):1862-7. Se 80% [78-82%] Density 1 98% Density 2 83% Density 3 64% Density 4 48% 2. DEMIST Digital Mammographic ImagingScreeningTrial ) Pisano ED et al. New Engl. J. Med 2005 The mammography sensitivity is related to the breast density • The higher the breast density, the lower the detection sensitivity1 • Variation of 64 % for breasts with a very high density to 87 % for very fatty breasts 2 7 mm
  • 10. Infra centimetric tumors and mammography 16 % 43 % 21 % 43 % Isolated microcalcifications cluster ( 43% ) Indicating an in situ lesion Rounded ( 20 %) or spiculated opacity (21%) Opacity and microcalcifications ( 16 % ) Inv Carcinoma Radial scar
  • 11. With mammography small cancers can be seen : microcalcifications Bi-Rads 3 BIRADS 4 ? • Analysis and detection of microcalcifications clusters on X-ray images Magnification views +++ • BIRADS : THE MORPHOLOGY is the first semiologic element to be taken into account before the evolvement Diagnostic pitfall 13 months DCIS comédo
  • 12. 1. Berg WA et al Cystic breast masses and the acrin 6666 experience. Radiol Clin North Am 2010;48:931-87 • These small rounded tumors should not be wrongly interpreted as intra-mammary lymph nodes. • You should be careful with stable lesions compared with the last medical balance and with lesions not found again under ultrasound. • Women with Family history ++ Misleading aspect of some lesions : rounded, regular, pseudo cystic image. With mammography small cancers can be seen (follow) : Round tumor with benign appearance 1 Diagnostic pitfall
  • 13. P David, J Le Sein Septembre 2004) Relation between size and tumoral growth Misleading rounded shapes Irregular outlines Bi-Rads 3 : if follow up ….  Opacity control at 4 months  Microcalcifications at 6 months • Growth speed • Intensity of the surrounding tissue reaction
  • 14. 2009 2009 Bi-Rads 2 ? Bi-Rads 3 ? Eric L Rosen and al Malignant Lesions Initially Subjected to Short-term Mammographic Follow-up Radiology 2002;223:221-228 2011 2011 Rosen: 4/12 opacities classified as node
  • 15. 3. Burrell HC, Sibbering DM, Wilson AR et al. Screening interval breastcancer : mammographic features and pronostic factors. Radiology 1996;199:811-7. 4. Andersson I, Ikeda DM, Zackrisson S et al. Breast tomosynthesis and digital mammography: a comparison of breast cancer visibility and BIRADS classification in a population of cancers with subtle mammographic findings. Eur Radiol. 2008 Dec;18(12):2817-25. 15 • Variation of the aspect according to the incidence or visibility under a sole incidence • The most frequent cause of interval cancers 3 • The breast tomosynthesis by reducing the tumor and gland superposition effects , should improve the sensibility versus the mammography 4 With mammography small cancers can be seen as : architectural distortion Diagnostic pitfall
  • 16.
  • 17.
  • 19. 4 radiologists 12631 women Cancer n = 121 Mammo 2D Mammo 2D + Mammo 3D 2 incidences Delta p False positives 6,1% 5,3% 15% P < 0,001 Cancers detection 121 soit 9,5 %o 77/121 6,1%o 101/121 8%o 24 27% P < 0,001 Invasive cancers detection 56 4,4%o 81 6,4%o 25 40% P < 0,001 Oslo trial Nov 2010 – Dec 2011 25 000 women Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population- based screening program. Skaane P et Al. Radiology. 2013 Apr;267(1):47-56.
  • 20. BIRADS 0 ? Doubt in mammography with an abnormality not accessible for a biopsy under ultrasound or stereotaxy
  • 21. Doubt in mammography ACR 4 Negative Predictive Value : Normal MRI allows to clear these images
  • 22. In front of a small tumor detected under ultrasound, the signs with the highest cancer positive predictive value are : The irregular shape : 62 % The orientation not parallel to the skin : 69 % The spiculated margins : 86 % 1 sign only : eliminate the benignancy Ultrasound signs : T1b > T1a Infra centimetric tumors and ultrasound The diagnostic value of the ultrasound is superior if the echography is guided by an abnormality detected on the mammography vs screening ultrasound
  • 23. 1. Iso-echogenic lesions (10 % of cancers) 2. Some high grade small cancers Posterior reinforcement of the ultrasonic beam due to their high cellularity Regular margins due to their fast growth Histology : Papillary carcinoma Infra-centimetric tumors and ultrasound Diagnostic Pitfall
  • 24. 1 2 3 Cysts , fibroadenoma and carcinoma ? Medularry Carcinoma Size 10 mm RH- Her2 + Post puncture
  • 25. Masses Enhancement (visible tumor in 3 planes > 5mm) Non mass Enhancement Foci each enchancement < 5mm Enhancing lesions Sensibility1,2 95-100 % in infiltrative Carcinoma 70-75 % in Ductal carcinoma In situ (DCIS) 1 Liberman L, Morris EA, Joo-Young Lee M et al. AJR Breast lesions detected on MR Imaging: features and positive predictive value. AJR 2002;179:171-178 2 Schelfout K, Van Goethem M, Kersschot E, et al. Preoperative breast MRI in patients with invasive lobular breast cancer. Eur. Radiol 2004;14:1209–1216. 3 Fabre Demard N, Boulet P, Prat X et al. Breast MRI in invasive lobular carcinoma: diagnosis and staging].J Radiol 2005;86(Pt 1):1027–1034. Infra centimetric tumors and RMI 73% Invasive carcinoma • DCIS • Invasive lobular carcinoma 3 Focal adenosis,Invasive carcinoma, DCIS, papilloma, fibroadenoma, LN…
  • 26. False negatives: the causes Weak tumoral angiogenesis and therefore low enhancement : • Histological type (5 % of the RMI FN)  Ductal Carcinoma In situ (DCIS)  Medularry Carcinoma Breast  Some Invasive Lobular Carcinoma (ILC) or with a consequent fibrous contingent • Small size cancers (Up to 3 % of false negative) Infra centimetric tumors and RMI Diagnostic Pitfall Enhancement  Absent (few or no angiogenesis)  Not seen (masked effect)  Wrong interpretation (Focus) Be careful with the mammary gland PHYSIOLOGICAL ENHANCEMENT particularly during the 2nd part of the menstruation ( RMI exam to be performed between the 7th and 13rd day of the menstruation)
  • 27. Background Parenchymal Enhancement : risk of hiding a small lesion minimal mild moderate marked Bi-Rads IRM 2013
  • 28. 28 • FOCI 1,2 CARACTERIZATION  Punctiform enhancements < 5 mm Not visible before injection +++ (T1 / T2) Unique or multiple • Up to 29 % of the patients presenting a suspicious lesion under mammography or ultrasound 1. Kuhl CK, Kreft BP, Hauswirth A et al. [MR mammography at 0.5 tesla. II. The capacity to differentiate malignant and benign lesions in MR mammography at 0.5 and 1.5 T].] Rofo 1995 Jun;162(6):482-91. 2. Brown J, Smith RC, Lee CH. Incidental enhancing lesions found on MR imaging of the breast. AJR Am J Roentgenol. 2001 May;176(5):1249-54. Infra centimetric breast carcinoma and RMI Mass enhancement : Invasive ductal Carcinoma Foci : Non mass enhancement < 5mm
  • 29. CCI SBR2 Re+ Rp- Her2 - Right Breast ultrasound 45% echo-guided biopsy 55 % of the lesions not found DeMartini et al. Utility of Targeted Sonography for Breast Lesions That Were Suspicious on MRI. AJR 2009;192:1128 SECOND LOOK ULTRASOUND
  • 30. VPP 96 % T > 20 MM VPP 62% T < 20 MM Microcalcifications NME > 5 mm
  • 31. Infra centimetric lesions : biopsies Pre-operatory diagnosis Difficult Extemporaneous  Malignity  Infiltrating ?  Prognosis factors  Grade  HER2 +++  Hormonal status  Lesions spreading
  • 32. Limits and difficulties of infra-centimetric lesions echo- guided microbiopsies ( T1a < 5 mm) Small size lesions? 3 -4 mm ? Visibility Post biopsy for small size lesions Pre-operatory localization X-ray ultrasound correlation X-ray of the operative element After biopsy of small lesions (< 5mm)
  • 33. “The mean size of such image-detected carcinomas is 11mm and 90% will be node negative.” “Errors in determining tumor size result from summing the sizes of the carcinoma • In multiple separate morcellated fragments of a resection • Or in the multiple separate fragments of a core biopsy procedure.” Issues with Tumor Size Assessment Michael Lagios, MD Seminars Breast Disease 2006, Volume 3, No. 9 T1a et T1b 20 mm 10mm
  • 34. Conclusion Small lesions ≤ 1 cm. Imaging Features. • Tumors with a good prognosis but up to 20% are N+ • Clinical exam + imaging : early diagnosis • Delayed diagnosis : Pitfall  Histological  Screening  Misleading appearance • Importance of a high quality imaging, knowing the limits. • Pre-operative diagnosis +++ • In case of doubt, sampling rather than close control
  • 35. Dr Jean-Yves SEROR (Paris, France) « Israeli-French Breast Cancer Update » Prevention, Detection and Treatment, Multidisciplinary approach Small lesions ≤ 1 cm. Imaging features.