Supraclavicular Lymph Nodes: From Halsted to Hortobagyi

1
Supraclavicular Lymph NodesFrom Halsted to
Hortobagyi
2
History

• HPI
• XX is a 46 year old white female who noted tender
  lump in left breast 6/02
• PMH
• significant for cysts in left breast
• last aspirated 4 years ago
• MEDS
• OCP
• SH
• no tobacco. () ETOH. Homemaker. 16 yr old
  daughter
• FH
• Father colon cancer

3
Surgeon visit

• ROS
• Menses age 13, q28 day cycles LMP 6/02
• G1P1, 30 yr old at first birth, did not nurse
• perimenopausal symptoms age 42 put on OCPs
• Had (-) mammograms since age 35
• PE
• Breasts symmetric, soft, no skin lesions,
  erythema, dimpling, niple inversion, discharge,
  ulcerations, crusting or cracking.
• ½ cm firm, smooth nodule in upper outer quadrant,
  at 200.
• No axillary or SCLAD

4
Diagnosis

• Diagnosis
• Simple Cyst
• Plan
• ultrasound
• aspiration
• and observation

5
Work up Hannibal Regional Hospital

• Ultrasound
• numerous simple cysts and a cluster at 200
  position where she felt her mass aspirated. One
  did not resolve.
• FNA Cytology 6/21/02
• ductular epithelial hyperplasia with
  papillomatosis, consistent with apocrine
  metaplasia. No evidence of malignancy
• Mammogram 6/17/02 (OSH)
• Isodense, oval mass with obscured margins seen in
  left breast at superior-lateral location. Benign
  appearing, Routine yearly mammogram recommended

6
10 days later

• PE
• Extensive ecchymosis over lateral L breast
• Area at 200 which is irregular, firmer than
  surrounding tissue, but without clear mass
• Feels mostly like prominent, dense,
  fibroglandular tissue without distinct margins
• Diagnosis
• S/p aspiration of left breast cyst
• Plan
• Follow up u/s in 4-6 months
• Monthly breast exams
• Yearly mammogram as scheduled

7
Follow up

• Pt started doing daily breast exams
• Mass was increasing in size
• Ultrasound guided biopsy done

8
Excisional Biopsy

• 8/6/02
• 0.9cm invasive adenocarcinoma, no DCIS
• Poorly differentiated
• 8/10/02
• She found palpable LN under left axilla
• Supraclavicular LN palpated also
• 8/13/02
• Decides to go to Siteman Cancer Center for
  further evaluation, work up and treatment

9
Office Visit

• Hard mobile 1x1cm SCLN on left
• 1 surgical scar at 200 left breast with 1cm
  area of firmness under scar
• Large palpable LNs under left axilla
• BJC Path review 1.2cm infiltrating ductal
  carcinoma, grade III/III, DCIS, high nuclear
  grade
• Diagnosis LABC
• Mammogram and u/s done

10
CC View
11
MLO View
12
Ultrasound

• gt3 axillary LNs (20mm, 23mm,13mm)
• Supraclavicular LN 15mm

13
A pectoralis major muscleB axillary lymph nodes
levels IC axillary lymph nodes levels IID
Infraclavicular lymph nodes levels IIIE
supraclavicular lymph nodesF internal mammary
lymph nodes
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AJCC Staging System (anatomic)
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TNM

• Our patient has SCLN as her only met
• AJCC 5th edition TMN T1N1M1
• Would you treat this woman as a MBC pt?

16
Halsted 1907

• He reviewed 210 operations
• 64 axilla(-) neck (-) 85 cured at 3 yr
• 110 axilla () Neck (-) 31 cured at 3 yr
• 44 axilla () Neck () 10 cured at 3 yr
• 5 at 5 yr
• Annals Surg Oncol 1907

17
Halsted 1907

• In 44 patients the glands of the neck as well as
  the axilla were involved. 3 of these (7) were,
  it seems, definitely curedbefore accepting the
  statement of anyone that he has cured a case of
  breast cancer with neck involvement,
  incontrovertable proof should be demanded. I
  confess that even if the microscopic findings
  were confirmed by an able pathologist I should
  still feel that an error had occurred, for
  example, in labeling the specimen

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Halsted 1907

• We should demand as further proof of cure in
  these positive neck cases that the patient live
  at least 5 years after the operation, or negative
  autopsy findings, a year or perhaps even 2 years
  thereafter. With these stipulation fulfilled I
  should still be skeptical as to the cure.

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AJCC 1st Edition(Data from 1960s)

• AJCC established in 1959
• First edition 1977
• SCLN was coded as N3, Stage III
• A review of 2000 cases in Manchester from
  1960-1967 showed N3 disease in 5 of cases
• 5 year survival for all patients was 50
• N0-1 disease 44-60
• N2-3 disease 9-14
• Sicher and Waterhouse Br J cancer 1973.

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1960s-1970s

• SCLN were considered an ominous sign
• Represent late stage of regional mets
• Cure was rare and most develop distant met within
  1 year of detection
• XRT and/or surgery became the Standard of Care

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Natural History and Survival of inoperable breast
cancer treated with Radiotherapy and radiotherapy
followed by radical mastectomy (1976)

• Bonnadonnas retrospective study
• Purpose to evaluate time of relapse and OS in
• 454 patients with T3-4, N1-3, M0
• treated w/ XRT from 1968-1972
• 133 pts also underwent surgery after XRT
• (those without SCLN, ICLN or radiation
  reactions)
• Zucali, Uslenghi, Kenda, Bonadonna Cancer 1976.

22
Results

• Characteristics of 454 patients
• N0 disease in 25 (117)
• N1-2 disease in 67 (303)
• N3 disease in 7 of patients (34)
• Mean age 56 years (28-84)
• 70 postmenopausal

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Results

• Local Control
• 50 had clinical CR
• 10 had SD
• 40 had changes in tissue so unevaluable
• Incidence of Relapse and OS from start of XRT
• 28 relapse at 18 months overall
• 50 if N() (no N3 specific category)
• Median survival 2.5 years for all pt
• If XRT and surgery then 4 years
• If XRT alone 2.1 years
• If supraclavicular involvement 1.4 years (not
  different from inflammatory 1.2 years)

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Survival in relation to presence and extent of
regional LNs
25
AJCC 3rd Edition(Data from 1980s)

• 795 patients referred to Radiation Dept of
  University of Wurzburg reviewed between 1978-1988
• 21 with SCLN at primary diagnosis (3)
• 38 with SCLN at recurrence (5)
• OS and clinical correlates were compared with
• 20 patients with M1 at diagnosis
• 278 patients with M1 during their disease course
  
• Kiricuta et al Int J Radiation Oncol Biol Phys
  1993.

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Patient Characteristics

• N3 M1 SCLNR METR Others
• Grp A C B D E
• 21 20 38 278 495
• F/U 1.9 1.9 4.4 4.1 4.2
• Age 58 64 55 54 58
• T3-4 65 65 23 30 15

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Survival

• N3 at dx M1 at dx
• 2 year 52 56
• 5 year 34 24
• SCLNR METR
• 2 year 50 46
• 5 year 16 16

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Survival Curves
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AJCC 3rd Edition

• Therefore, AJCC 3rd edition 1988 made
  supraclavicular LN M1, Stage IV disease

30
Meanwhile..at MDACC

• They thought Stage III in 2nd edition was too
  variable because N2 pts got surgery and had
  30-45 5 yr OS and N3 pts were considered
  nonoperable and had 10-20 5 yr OS
• 174 pts with LABC 1974-1985
• 48 pts had IIIa (N1-2) and 126 pts with IIIB(T4
  or N3)
• Neoadjuvant chemo with FACx3
• then surgery if no CR
• then /- XRT (50Gy10Gy boost to scar50Gy SCLN)
• then FAC until 450-500mg/m2 Adria
• then CMF for 2 years
• Hortobagyi et al Cancer 1988

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Results

• Median age was 51 years
• Median F/U was 59 months
• 30 were ER()
• ORR to neoadjuvant chemo---71
• Only 65 pts got the entire 2 year program
• 9 of IIIa and 91 of IIIb (dismal compliance)
• so in 1980 they switched to a 9 month program
  instead!
• Hortobagyi et al Cancer 1988

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Results

• DFS at 5 years 84 for IIIA
• 33 for IIIB
• OS at 5 years 84 for IIIA
• 44 for IIIB
• OS at 10 years 56 for IIIA
• 26 for IIIB
• 26 of N3 pts developed distant mets
• Hortobagyi et al Cancer 1988

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Supporting Studies

• Chinese Study 1995
• 2805 cases of breast cancer between 1954-77
• 3.5 had SCN met at diagnosis (98 pts)
• Patients divided into 4 groups
• Surgery with postoperative adjuvant
  chemotherapy/XRT
• Radiation and chemotherapy
• Chemotherapy
• No treatment.
• 5 year OS Group I 18 (8/44)
• Group II 5 (1/21)
• Group III/IV 0
• Results seem to indicate that more aggressive
  multi-modality treatment of breast cancer with
  ipsilateral SCLN metastases is indicated to
  expect better survival.
• These results are dismal however when compared
  with other studies
• Ning L et al. Chinese Journal of Oncology
  17(2)139-41, 1995 Mar.

34
AJCC 6th Edition(Data from Long Term Results of
Combined-Modality Therapy at MDACC)

• 598 patients with LABC treated on 3 prospective
  protocols between 1974-1991
• 70 patients with LABCSCLN (regional Stage IV
  LABC)
• Neoadjuvant chemo
• Study 1 FACx3 , surgery, level I II ALND, XRT
• then FAC until Adria maxed then CMF
• Study 2 VACP x3, surgery, VACPx5, XRT
• Study 3 FACx4 with A as civi,surgery,FACx4,XRT,
  TMX
• Brito RA, Valero V et al JCO 192001

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Results

• These patients compared with 239 IIIB LABC
  patients treated on these same trials
• Median age 49 Median F/U 11.6 years
• RR to neoadj 89 (21CR)
• Local-regional control rate 81
• Median duration of survival was 2.5 years
• DFS 34 at 5 years OS 41 5 year
• 32 at 10 years 31 10 year
• Not significantly different from IIIB disease
• Brito RA, Valero V et al JCO 192001

36
OS for Stage IIIB and Regional Stage IV
37
OS for Regional Stage IV LABC and Stage IV BC
treated with AC
38
Revision of the American Joint Committee on
CancerStaging System for Breast Cancer

• Journal of Clinical Oncology 2002

39
The new staging system, which will be adopted in
January 2003, envisions a new stage, IIIC, and
will have significant impact on the treatment
recommendations.
Our Patient therefore is T1N3cM0 or stage
IIIc
40
Our Patient

• Bone scan, CT scans all negative
• ER/PR/HER2neu (-)
• Neoadjuvant chemo
• Epirubicin 75 mg/m2
• Taxotere 75 mg/m2
• She had clinical resolution of breast mass after
  two cycles, and decrease in axillary LAD after
  three. Her SCLN is less than 1 cm.
• Lumpectomy,ALND and XRT planned
• Adjuvant chemo pending pathology at surgery