Breast Cancer: Specific Situations

Diagnosis And Treatment Of Patients
With Primary And Metastatic Breast Cancer
© AGO
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Guidelines Breast
Version 2013.1
Breast Cancer:
Specific Situations
Breast Cancer:
Specific Situations
© AGO
e. V.
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Guidelines Breast
Version 2013.1
www.ago-online.de

Versions 2005-2012:
Dall / Gerber / Göhring / Harbeck /
Huober / Janni / Loibl / Lück / Lux / Maass
/ Mundhenke / Oberhoff / Rody / Scharl

Version 2013:
Fersis / Friedrich
Breast Cancer:
Specific Situations
© AGO
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Guidelines Breast
Version 2013.1

Young patients

Pregnancy-associated BC

Elderly patients

Male patients

Inflammatory BC

Occult Primary [Carcinoma of unknown
primary (CUP)]

Paget´s disease

Malignant Phyllodes Tumor

Sarcomas
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Breast Cancer in
Young Women ≤ 35 Years
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e. V.
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Guidelines Breast
Version 2013.1

Aggressive biological behavior
2a
B

Benefit from chemotherapy
1b
A
++

Benefit from endocrine therapy
1b
A
++

Endocrine therapy (TAM) if possible 5-10 y
1b
B
++

Benefit from trastuzumab
2b
B
++

Benefit from CT induced temporary amenorrhoea 2b
B
+/-
1a
A
-
GnRHa as ovary protection 2 weeks prior CT
www.ago-online.de

Surgery like ≥ 35 y (in particular BCT)
2b
B
+

Stage II–III benefit from PMRT
2b
C
+

Genetic and fertility counseling
2b
B
++
Breast Cancer During Pregnancy*
or Breast Feeding
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Guidelines Breast
Version 2013.1

Breast imaging & biopsy like in non-pregnant
4
C
++

Staging: ultrasound, chest X-ray if indicated
5
D
+/-

Surgery like in non-pregnant patients
4
C
++

Sentinel node excision (technetium only)
4
C
+
SNE during 1st trimester
5
D
+/-
Sensitivity and specificity not established
(during lactation); breast feeding should
be avoided for 24 hrs
4
C
++
Blue dye (has not been tested in
pregnant animals or humans)
4
C
--

www.ago-online.de

* Participation in register study recommended
Breast Cancer During Pregnancy*
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Guidelines Breast
Version 2013.1


www.ago-online.de


Radiation therapy during pregnancy
(Neo-)adjuvant chemotherapy only
after first trimester
(indication as in non-pregnant)
 AC, FAC (FEC)
 Taxanes
 MTX (e.g. CMF)
 Endocrine treatment
HER2-neu targeted treatment
Bisphosphonates
4
2b
2b
4
4
3a
4
C
-
B
B
D
D
C
D
++
++
+
----
* Participation in register study recommended
Breast Cancer During Pregnancy*
© AGO
Oxford / AGO
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in der DGGG e.V.
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Guidelines Breast
Version 2013.1



www.ago-online.de

Delivery should be postponed until sufficient
fetal maturation (avoid iatrogenic prematurity) 2b
Termination of pregnancy does not improve
maternal outcome
3b
Delivery mode like in healthy women,
4
avoid delivery 3 weeks from prior
chemotherapy
If further systemic therapy is needed after
delivery, breast feeding may be contraindicated depending on drug toxicities
5
C
++
C
C
++
D
++
* Participation in register study recommended
Pregnancy Associated
Breast Cancer*: Outcome
© AGO
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Oxford
Guidelines Breast
Version 2013.1
LoE
BC during pregnancy / lactation
 Adequate
treatment is essential
3a
Pregnancy and lactation after BC
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
Outcome not compromized
3a
* Participation in register study recommended
Geriatric Assessment
© AGO
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Guidelines Breast
Version 2013.1
•
•
•
No specific algorithm is available
Ability to tolerate treatment varies greatly („functional
reserve“)
Comprehensive geriatric assessment (CGA) describes a
multidisciplinary evaluation of independent predictors of
morbidity and mortality for older individuals
•
•
•
www.ago-online.de
•
Physical, mental, and psycho-social health
Basic activities of daily living (dressing, bathing, meal preparation,
medication management, etc.)
Living arrangements, social network, access to support services
Assessment tools:
•
•
•
•
Charlson Comorbidity Index (widely used; good predictor over a 10year period)1
12 prognostic indicators to estimate 4-year mortality risk
Short screening tests (more qualitative evaluation)
IADL, G8 (IADL = The Lawton Instrumental Activities of Daily Living
Scale with 8 domains of function, that are measured)
Treatment for Fit Elderly Patients
(Life Expectancy > 5 yrs. and Acceptable Comorbidities)
© AGO
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LoE / GR
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in der DGGG e.V.
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Guidelines Breast
Version 2013.1

Geriatric assessment
2b
B
++

Treatment according to standard
2a
C
++

Surgery similar to „younger“ age
2b
B
++

Endocrine treatment (endocrine resp.)
1a
A
++

Chemotherapy
www.ago-online.de

< 70 years
1a
A
+

> 70 years (especially N+, ER/PgR-)
2a
C
+*
1a
A
+
2b
B
+/-
2b
C
+

Radiotherapy

Omit Radiotherapy after BCT In low risk**
With endocrine treatment

Trastuzumab
*Study participation recommended
**Population > 70 y, hormone receptor positive and if endocrine therapy is planned (CAVE: increased risk local
recurrence)
Treatment for Frail Patients
(Life Expectancy <5 yrs, Substantial Comorbidities)
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Guidelines Breast
Version 2013.1

Reduced standard treatment

Options extrapolated from trials in elderly:
++
No breast surgery
(consider endocrine options)
2b C
+

No axillary clearing (≥ 60 y, cN0, Rec pos)
2b B
+

No radiotherapy ( ≥ 70 y, pT1, pN0, Rec pos) 2b C
+

Hypofractionated radiotherapy
2b C
+

No chemotherapy >70 years and negative
risk-benefit analysis
2b C
+

www.ago-online.de
2b C
Male Breast Cancer: Diagnostic
Work-Up and Loco-Regional Therapy
© AGO
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Guidelines Breast
Version 2013.1


Diagnostic work up as in women

Mammography

Ultrasound
Standard-surgery: Mastectomy


Sentinel-node excision (SNE)
4
3b
2b
4
2b
C
C
B
C
B
+
+/++
++*
+
4
C
+
Radiotherapy as in women
(consider tumor breast relation!)
www.ago-online.de


Genetic counselling if one additional
relative affected (breast/ovarian cancer)
Screening for 2nd malignancies
according to guidelines
2b B
++
GCP
++
*Participation in register study recommended
Male Breast Cancer:
Systemic Therapy
© AGO
Oxford / AGO
LoE / GR
e. V.
in der DGGG e.V.
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in der DKG e.V.
Guidelines Breast
Version 2013.1

Adjuvant chemotherapy as in women
2a
B
++

Trastuzumab
5
D
+*

Endocrine therapy
4
D
++
- Tamoxifen
2b
B
++
- Aromatase inhibitors (adjuvant)
2b
B
-
- Aromatase inhibitors (metastatic BC)
4
C
+/-
- GnRHa and AI (metastatic BC)
4
C
+/-
- Fulvestrant (metastatic BC)
4
C
+/-
4
C
++
www.ago-online.de

Palliative chemotherapy as in women
*Participation in register study recommended
Inflammatory Breast Cancer (IBC, cT4d)
© AGO
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Guidelines Breast
Version 2013.1



www.ago-online.de

In case of invasive BC and clinical signs of
inflammation (> 1/3 of the breast affected)
determine stage cT4d
Staging
Skin punch biopsy (at least 2; detection rate < 75%)
Preoperative chemotherapy
 Regimens as in non-inflammatory BC
 Anthracycline and taxane-based
 In HER2 + disease addition of trastuzumab
Mastectomy after chemotherapy

Sentinel excision only
Radiotherapy
Postoperative systemic therapy as in
non-inflammatory BC



Breast conserving therapy in case of pCR
Oxford / AGO
LOE / GR
2c
2c
2c
B
B
B
++
++
+
++
2b
2b
2c
2b
3b
2c
B
B
B
C
C
B
++
++
++
+/-++
4
C
++
Axillary Metastasis in Carcinoma
of Unknown Primary (CUP)
© AGO
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Guidelines Breast
Version 2013.1
www.ago-online.de

Mammography / Breast ultrasound
3
B
++

Breast MRI
3
B
++

Staging (CT thorax / abdomen, thyroid
sonography, ENT investigation)
3
B
++

PET / PET-CT
3b B
+/-

Gene expression profiling (e.g. CupPrint™)
2c B
+/-

ER, PgR, HER2
5
D
++

Axillary dissection
3a C
++

Systemic treatment according N+ tumor
3a C
++

Mastectomy if breast MRI is negative
3a C
-

Breast irradiation if breast MRI is negative
3b C
+/-

Irradiation of regional lymph nodes according to
breast cancer guidelines
3b B
+
Paget´s Disease of the Breast
© AGO
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Guidelines Breast
Version 2013.1
Histological verification
 Mammography, sonography


www.ago-online.de
4
5
1c
2b
2b
D
D
B
B
B
++
++
+
++
+
+/-
5
D
++
Surgical resection only, no adjuvant radiotherapy 4
D
++


Surgery must include NAC (R0)

Wide excision (like DCIS) + radiotherapy

Sentinel-node excision (SNE)
Paget´s disease with underlying disease (e.g.
invasive breast cancer, DCIS)


MR of the breast if other imaging negative
Therapy according to standard of the underlying
disease
Isolated Paget´s disease of the NAC (<5%):

Malignant Phyllodes Tumor
© AGO
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e. V.
in der DGGG e.V.
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Guidelines Breast
Version 2013.1





Complete (wide) local excision or MRM
SNE / Axillary dissection in cN0
Staging
Systemic adjuvant therapy (chemo, endocrine)
Adjuvant radiotherapy

www.ago-online.de


if T ≥ 2 cm (BCT) or T ≥ 10 cm (mastectomy)
2b
4
5
4
4
2b
B
C
D
C
C
C
++
-++
--+/-
4
4
C
C
++
+/-
4
C
++
Treatment of local recurrence

R0 resection

Radiotherapy, chemotherapy after R1 resection
Distant metastases (very rare)

Treatment like soft tissue sarcomas
Sarcoma / Angiosarcoma of the Breast
(Note: very aggressive!)
© AGO
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Guidelines Breast
Version 2013.1
Treatment of Primary Disease:

Mammography, Sonography to determine extent of disease

Preoperative MRI to determine extent of disease

Diagnosis by core biopsy

Diagnosis by FNB

Staging

Prognostic factors: size, grade, margins

Surgery with wide clear margins
3a
3a
3a
3a
4
3a
3a
3a
3a
3a
C
C
C
C
D
C
C
-++
++
-++
++
++
C
+/-
C
C
+/-
4
C
+/-
Treatment of Local Recurrence:

R0 resection

Radiotherapy, chemotherapy after R1 resection
4
4
C
C
++
+/-
Distant Metastases / Unresectable Tumors:

Treatment like soft tissue sarcomas

Paclitaxel weekly / liposomal doxorubicin (in angiosarcoma)

Antiangiogenic treatment

Trabectidin (after anthracycline/ ifosfamide failure in leiomyosarcoma)
4
2b
4
2b
C
B
C
B
++
+
+/+



breast-conserving therapy if feasible
Axillary dissection if cN0
Adjuvant chemotherapy, radiotherapy

www.ago-online.de
Oxford / AGO
LOE / GR
adjuvant chemotherapy (anthracycline-based), radiotherapy
in case of high risk (grade II-III, size > 5 cm, R1)