Tumor Board

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Tumor Board

• 9/23/08

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Tumor Board

• EF
• 60 y/o F with known history of Left lower
  extremity melanoma with lymph node metastases,
  presented with a palpable mass in the left breast
• The patient denied any pain form the area
• Denied fever, chills, as well as Nausea/
  Vomiting/ Diarrhea

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Tumor Board

• Vitals- AVSS
• CVS- RRR
• Lung- CTAB
• Abd-soft, ND, NT, BS
• Breast- Left Upper outer quadrant 3x1 cm
• Firm, fixed, no mobility, minimal tenderness
• No nipple discharge, No nipple retraction

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Tumor Board

• Mammogram- no occult disease, mass suspicious for
  malignancy
• FNA- inconclusive
• A/P
• To OR for Excision of Mass

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Tumor Board

• PreOperative Dx- Mass in Left Breast
• PostOperative Dx- Left Breast Adenocarcinoma
• Procedure-Left breast lumpectomy with positive
  sentinel lymph (positive) and axillary lymph node
  dissection
• Level I, II and III
• EBL-minimal
• Complications-none

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Tumor Board

• 1976, Bonadonna and his colleagues published the
  results of their landmark trial of adjuvant
  chemotherapy for breast cancer.
• They showed that 12 months of postoperative
  chemotherapy consisting of cyclophosphamide,
  methotrexate, and fluorouracil (CMF)
• decreased the risk of recurrence of breast cancer
  in women with positive axillary lymph nodes.

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Tumor Board

• Since then, many trials have been undertaken to
  answer important questions about adjuvant
  chemotherapy
• What is the optimal number of drugs?
• What are the most advantageous doses of the
  agents used for adjuvant chemotherapy?
• How long should they be administered?
• What is the role of Adjuvant Chemotherapy in
  Postmenopausal Women with lymph nodes?

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Role of Adjuvant Chemo in Postmenopausal Women
with lymph nodes

• Overall the current thinking is
• Adjuvant chemotherapy offers negligible benefit
  to receptor-positive, postmenopausal women
• Legitimate end points for discussion included
  survival as well as quality-adjusted time without
  symptoms or toxicity (Q-TwiST).
• Other considerations included cost of therapy as
  it relates to collective benefit
• The following analyzes how we got to this point!

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Adjuvant Chemotherapy

• Early Breast Cancer Trialists' Collaborative
  Group (EBCTCG), Gelber and colleagues2
  concluded that adjuvant chemotherapy did not add
  to survival.
• Collectively, the EBCTCG trials enrolled more
  than 15,000 women.
• An 8 gain in absolute survival at 15 years
  favored those receiving combination treatment
• translated into a 19 reduction in relative risk
  of relapse with a relative death risk reduction
  of 11.
• Unfortunately, many of these women had estrogen
  receptor (ER)-negative tumors and were
  premenopausal, so the absolute benefit in
  postmenopausal ER-positive women could not be
  measured accurately

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Adjuvant Chemotherapy

• 2001 EBCTCG update by Cole and colleagues3
  reviewed the results of 47 studies with more than
  18,000 women enrolled.
• Women older than aged 50 years with poor estrogen
  or positive ER expression were analyzed with a
  median follow-up of 10 years.
• Women with ER-positive tumors who received both
  chemotherapy and tamoxifen enjoyed a 6.3-month
  relapse-free survival advantage with a 2.8-month
  overall survival advantage over women given only
  tamoxifen.
• Women with ER-negative tumors derived a 5.5-month
  relapse-free survival advantage with a 3.7-month
  overall survival advantage over those receiving
  tamoxifen alone.
• Cole and his collaborators concluded that
  regardless of ER status, the benefits of
  combination chemoendocrine therapy were
  essentially the same.

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• Highlighting individual cases
• Danish Breast Cancer Cooperative Group, which
  enrolled nearly 700 postmenopausal women in each
  of 3 treatment arms, one with tamoxifen alone,
  another with chemotherapy plus tamoxifen, and a
  third with radiation plus tamoxifen.
• At a 12-year median follow-up, no differences
  were observed between the treatment arms

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Adjuvant Chemotherapy

• National Surgical Breast and Bowel Project
  (NSABP) 20,
• showed only a 2 survival advantage at 5 years
  with chemotherapy plus tamoxifen vs tamoxifen
  alone in ER-positive tumors, but failed to show
  any benefit whether patients were postmenopausal
  or not.

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Adjuvant Chemotherapy

• NEWER trials
• International Breast Cancer Study Group IX and
  NationalSurgical Breast and Bowel Project
  (NSABP-20) presented conflicting results.
• The negative findings of the former trials may be
  attributable to the shorter duration of
  chemotherapy given, the fact that CMF may be more
  effective in patients with metastatic breast
  cancer, and differences in tumor biology (with a
  greater percentage of well-differentiated tumors
  found in older women).
• If one stratifies patients according to strict
  biomarker equivalency, response to chemoendocrine
  therapy equalizes across age groups.

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Adjuvant Chemotherapy

• Chemoendocrine therapies employing
  anthracycline-based regimens have been shown to
  improve disease-free and overall survival in
  NSABP-16 and the French Adjuvant Study Group
  (FASG)-07.5
• In the Breast Cancer Intergroup Trial 0100, which
  randomized 1500 patients to receive
  cyclophosphamide, doxorubicin, and 5-fluorouracil
  (CAF) plus tamoxifen vs tamoxifen,
• 32 of patients were aged 65 years or older
• 13 were older than 70 years of age.
• Disease-free survival
• at 5 years was 76 in the CAF-plus-tamoxifen arm
  vs 67 in the tamoxifen-alone arm
• 5 overall survival difference was seen at 5
  years

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Adjuvant Chemotherapy

• After review of literature many questions arise
• If there a significant advantage in survival with
  postmenopausal chemotherapy, at what cost do
  postmenopausal women make these gains in
  mortality
• Quality of life
• Complications of chemo
• Cost of therapy
• Problem with studies
• Difficult to objectively compare
• Pt have different stages of breast ca
• Different co-morbidities
• Differnece in age- young vs old postmenopausal

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Adjuvant Chemotherapy

• In general
• No significant overall survival differences have
  been shown in ER-positive, postmenopausal women
  whether they were treated with combination
  chemoendocrine therapy or endocrine therapy
  alone.
• Furthermore, no differences in quality of life
  (Q-TwiST) were recorded, particularly in the
  EBCTCG studies. Costs and toxicity for women
  undergoing chemotherapy are assuredly higher
• Overall
• Newer trials on the horizon with promising
  results contradicting some of the previous
  literaute
• However, many of these studies are being analyzed

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Can Radiation course in BCT be Shorter?

• Whalen et al.
• ASTRO American Society for Therapeutic Radiology
  And Oncology Meeting
• 1,234 women with node-negative invasive breast
  cancer from April 1993 through September 1996 and
  randomized them to the shorter duration of
  radiation therapy or to standard treatment
• The rate of recurrence of breast cancer after 10
  years of follow-up was 6.2 if women got 50 Gray
  of radiation over three weeks, according to
  Whalen et al
• In women who got the standard 42.5 Gray over five
  weeks, the rate of recurrence was 6.7.

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Can Radiation course in BCT be Shorter?

• Because of the higher doses of radiation at each
  treatment in the shorter course, he said, the
  concern had been that there would be a higher
  rate of late side effects.
• But in fact, he said, there was little difference
  between the arms 10 years later
• The absolute difference between the treatment
  arms in the risk for local recurrence was 0.5.
• 70 of patients getting the short course had a
  good or excellent cosmetic outcome, compared with
  71 in the longer arm, for an absolute difference
  of 1.5.

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Can Radiation course in BCT be Shorter?

• The occurrence rate of moderate and severe late
  radiation morbidity to the skin was
• 6 in the short course
• 3 in the long course,.
• None of the differences reached statistical
  significance.
• In Canada
• shorter course has already become standard
  practice, because it offers a more convenient
  treatment schedule at about two-thirds of the cost

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Can Radiation course in BCT be Shorter?

• A shorter course of radiation therapy with a
  lower dose following lumpectomy is as effective
  as the longer standard adjuvant therapy for
  breast cancer

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Level I and Level II Dissection

• It well known in current literature that
  regarding lymph node dissection of the breast
• level-III dissection results in a longer
  operation time with greater blood loss than
  level-I II alone
• Complications
• axillary vein thrombosis
• Lymphedema
• Nerve injury
• Also, there is no improvement in the survival
  rate with level III dissection.

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Level I and Level II Dissection

• Level I- Inferior Lateral to pectoralis minor
• Level II- Posterior to pectoralis minor
• Level III- Medial to pectoralis minor

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Level I and Level II Dissection

• Kodama H, Nio Y, Iguchi C, Kan N. Ten-year
  follow-up results of a randomised controlled
  study comparing level-I vs level-III axillary
  lymph node dissection for primary breast cancer.
  Br J Cancer. 2006 Oct 995(7)811-6.
• randomised study compared the treatment results
  of level-I II vs level-III dissection in T1/2/3
  and N0/1a/1b (1987 UICC classification) breast
  cancer without distant metastasis.
• Between 1995 and 1997, 522 patients were
  enrolled, and 514 were eligible.

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Level I and Level II Dissection

• Stratified into breast-conserving surgery or
  mastectomy, and then further stratified into
  level-III dissection (group-A, n258) or level-I
  dissection (group-B, n256).
• All patients were given oral 5-fluorouracil at
  200 mg day-1 and tamoxifen at 20 mg day-1, daily
  for 2 years

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Level I and Level II Dissection

• Group-A resulted in a significantly longer
  operation time (77.0 vs 60.5 min, Plt0.0001) and
  significantly larger blood loss (62.1 vs 48.1 ml,
  Plt0.0001) than group-B, but in no significant
  differences in the frequencies of arm oedema and
  shoulder disturbance
• Group-A resulted in a significantly larger number
  of dissected nodes than group-B (18.7 vs 14.8,
  Plt0.0001), but in no differences in the number of
  involved nodes (1.54 vs 1.44).

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Level I and Level II Dissection

• There were no significant differences in the
  10-year overall and disease-free survival rates
  89.6 and 76.6 for group-A vs 87.8 and 74.1 for
  group-B, respectively.
• Overall, there is no benefit to level III
  dissection compared to level I II