Locally advanced breast cancer is stage III breast cancer characterized by large primary tumors with involved lymph nodes. Key points: - Suspensory ligaments can become invaded, leading to skin dimpling. Lymph nodes are divided into groups for staging. - Axillary nodes are the primary drainage site and are divided into levels based on relation to pectoralis minor muscle. - Internal mammary nodes also commonly involved with medial/central/lower tumors. - Locally advanced breast cancer is usually treated with neoadjuvant chemotherapy to downstage the tumor, followed by surgery and radiation. Molecular subtyping aids treatment planning.

1. Locally
Advanced
Breast Cancer
Presented by- Dr. Rashmi
Moderated by- Dr. Pavan Kumar

4. Suspensory ligament/Coopers ligament-
These run between superficial fascia(attached to skin)and the deep fascia(covering the
pectoralis major and muscles of Chest Wall)
Invasion of these ligaments by tumor leads to skin dimpling

5. Lymph node
groups
1. Anterior (pectoral)group
2. Posterior (sub scapular)group
3. Lateral group
4. Central group
5. Apical group
Inter pectoral group
Rotter’s nodes

6. Axillary lymph nodes
• Predominant lymphatic drainage of the
breast
• Divided in three levels based on relation to
Pectoralis minor muscle
• Level I – Caudal and lateral to the muscle
• Level II –Beneath the muscle
• Level III –Cranial and medial to the muscle;
Level I and II are routinely removed in axillary
dissection.

7. Internal mammary lymph node chain (IMC)
• These are intra thoracic located in
para sternal space and usually lie 3-
4 cm lateral to mid line
• Breast cancers in medial, central or
lower breast more commonly drain
to IMC( in addition to axilla) than
those occurring in lateral and upper
quadrants

9. RISK FACTORS

11. Why knowing about Breast carcinoma is important ?
• Breast carcinoma is the most common cancer of women in the world and also in India
• In spite of its incidence the mortality rate is declining since 1991 suggesting a benefit from
a) Awareness
b) Screening
c) Early diagnosis &
d) Effective treatment

14. Staging

18. Stage Grouping
Stage T N
0 Tis N0
IA T1 N0
IB T0-1 N1mi
IIA T0-1 N1
T2 N0
IIB T2 N1
T3 N0
IIIA T0-3 N2
T3 N1
IIIB T4 Any N
IIIC Any T N3
IV Any T Any N
M1

20. Locally Advanced Breast Cancer
• Stage III ca breast with –
• T3, T4a,b,c,d tumor and
• Involved nodes (N)
• clinical N2a, b, cN3a,b,c;
• pathological N2, N3
Inflammatory breast carcinoma is a type of LABC
Both Clinical And
Pathological Stage III

21. Clinical Presentation
• Large tumor palpable
• Skin edema- peau’d orange
• Satellite skin nodules
• Skin ulceration
• Tumor fixation to the chest wall
• Fixed axillary nodes
• Axillary
• Infra-clavicular and
• supraclavicular adenopathy

22. • History and physical examination
• Pathological assessment
• Trucut Biopsy
• FNAC from any doubtful LN
• IHC Status
• Patient profile
• Imaging
• Chest x-ray
• USG W/A
• Bone Scan
• PET CT scan whole body
• MRI Brain in c/o doubt
• Mammography of opposite Breast
Investigations

23. Nomenclature
• Surgical specimen report Post NACT – ypT, ypN
• But for M1 disease it is M1 throughout the course- before & after t/t.

24. Management of breast cancer
• Constitutes of Multi-modality approach:
1. Surgery
2. Radiotherapy
3. Chemotherapy
4. Hormone therapy
5. Targeted therapy

25. Locally Advanced Breast Cancer ( LABC )
LABC
Inoperable Operable
NACT Surgery
Surgery Adjuvant CT/RT +/- HT

28. NCCN

29. Why Neo Adjuvant Chemotherapy
1. NACT has a correlation between response to therapy and long term outcomes.( i.e.
patients with pCR after NACT have Increased DFS).
2. It downstages the tumor.
3. Improves surgical resectability.
4. Provides information regarding the tumor response to chemotherapy.
5. Highly proliferative tumors like Luminal B, Luminal Her2neu, Triple negative are
highly sensitive to chemotherapy than low proliferative counterparts.
Patients who do not respond
to NACT , should be offered
non cross resistant regimen
or procced directly to local
therapy.
Tumors that are resistant to
one CT regimen usually tend
to be broadly chemo-
resistant, posing a
management challenge

30. Choice of chemo regimen in NACT

31. • Poly-chemotherapy regimens with Anthracycline & Taxane are preferred
• Anthracycline based regimens are better than the CMF regimen
• AC + Taxane is the most effective regimen.
NACT – Her2neu Negative:

36. Benefit with NACT
Trial Randomisation DFS OS Remarks
NSABP B18
[1988-93]
AC adjuvant or
neoadjuvant?
4# AC  Sx vs
Sx  4# AC
67% both [5 yr]
58% vs 55% [8 yr]
42 vs 39% [16 yr]
NS
81 vs 80% [5 yr]
72% both [8 yr]
55% both [16 yr]
• Median F/U 16 yrs [2008]
• For OBC
• pCR: significant predictor for
DFS/OS
• BCS rate 68 vs 60% [SS]
• pCR 13%
 No DFS/OS benefit with NACT as compared to adjuvant Chemotherapy
 Increased rates of BCS
 pCR is a significant predictor of DFS/OS
 9 yr DFS: 75% [complete responders] vs 58% [partial responders]
 9 yr OS: 85% [complete responders] vs 73% [partial responders]

37. HORMONAL THERAPY IN NEO ADJUVANT SETTING
◦ Mostly used in patients with locally advanced breast cancer who are deemed unfit for systemic CT,
post menopausal and ER/PR positive tumors.
◦ Responses are slower than neo adjuvant chemotherapy
◦ Rates of pathological complete response (pCR) are also less than neo adjuvant chemotherapy)
◦IMPACT Trial :
◦Immediate Pre operative Anastrazole, Tamoxifen or Combined with Tamoxifen Trial
◦330 Estrogen receptor positive post menopausal females randomized to 1:1:1
◦Response rates of 36% to 39%
◦Only 1% to 3% achieving a clinical complete response
◦Result : Rates of breast conservation after 3 months of neo adjuvant hormone
treatment were highest in the Anastrozole alone arm.
But in a specific cohort patients like post menopausal, ER/PR +ve especially luminal A

38. ◦ PROACT Trial : Pre operative “Arimidex” compared to Tamoxifen Trial
◦ In post menopausal pts with T2/3/4b, N0-2, M0.
◦ Objective responses for Anastrozole and tamoxifen occurred in 39.5% and 35.4%
of patients, (ultrasound measurements), and 50.0% and 46.2% of patients
respectively (caliper measurements).
◦ Result : Anastrozole is an effective and well-tolerated preoperative-therapy,
producing clinically beneficial tumor downsizing and reduction in tumor
volume.
HORMONAL THERAPY IN NEO ADJUVANT SETTING

39. Breast conservation in LABC
• Breast conservation is dependant on extent of tumor present after completion of NACT.
• Complete clinical and radiological assessment to be done to see the eligibility of BCS.
• Features predicting high rates of LRR and IBTR:
a) Advanced nodal involvement at diagnosis
b) Residual tumor larger than 2 cms
c) LVSI
Complete clinical or radiographic response may still be associated with residual disease on
pathologic exam. This may be due to persistence of scattered areas of invasive cancer in a
background of tumor that has been partially eradicated in a fragmented fashion, or of
intraductal cancer, which is not affected by CT

40. Breast Conservation: The TMH Experience
• January 1998 to June 2009
• n= 1402 , age 23–76 years, 47.9% postmenopausal
• 63% ER -ve, 62.5% PgR -ve, 20% CerbB2 positive
• Anthracycline-based chemotherapy
• Taxanes given upfront [5%], CMF [1.5%]
• Response: 79.2%
• pCR: 8%
• BCS Rate: 30.4%
• Factors predicting pCR
• Non expression of ER/PR [HR 5.37]
• Presence of LVE [HR 0.25]
• Younger age [HR 1.04]
• Absence of skin involvement [HR 2.05]
• Local Relapse rate: 8% at 30 m

41. • Mobile axillary node –N1
• No chest wall fixity- upto T3
• Small skin involvement
Operable subsets of LABC

42. Breast conservation

43. Indications
1. Low grade tumors
2. Stage I & II
3. Mono centric tumors
4. Not a high risk patient
Contra indications
1. Stage III & IV
2. Multicentric/multifocal disease
3. High risk patients
4. Previously irradiated thorax
5. Pregnancy
Breast conservation

44. Mastectomy is indicated in LABC

45. 1. Simple mastectomy
2. Skin sparing mastectomy
3. Nipple sparing mastectomy
4. Radical mastectomy
5. Modified radical mastectomy
6. Extended radical mastectomy
7. Toilet mastectomy
Types of mastectomy

46. Breast Surgery
Surgery Extent of resection
Segmental Mastectomy,
Lumpectomy, tylectomy
Primary tumor + margin of breast tissue
Total/Simple Mastectomy Breast alone
Modified Radical Mastectomy Breast + Axillary Level I/II Dissection
Radical Mastectomy Breast + Pec Major + Axillary Level I/II
Extended Radical Mastectomy Breast + Pec Major+ Axillary Level I/II + IMN ± Level III Axillary LN
Skin Sparing Mastectomy TM or MRM with preservation of a significant component of
native skin to optimize aesthetic result of an immediate
reconstruction

47. COMPLICATIONS OF M.R.M
a) Injury of axillary vein/ vessel thrombosis
b) Seroma—50-70%
c) Shoulder dysfunction 10%
d) Pain (30%) and numbness (70%)
e) Flap necrosis/infection
f) Lymphoedema (15%) and its effect on QOL
g) Axillary hyperaesthesia (0.5-1%)
h) Winged scapula
i) Pectoral muscles atrophy if medial and lateral pectoral nerves are injured
j) Weakening of internal rotation and abduction of shoulder occurs due to injury
to thoracodorsal nerve
33

48. Adjuvant CT
All patients should receive chemotherapy, but
CT may be omitted in pts - Age >/= 70 yrs , T1 lesion , Hormone + ve &Comorbidities

49. Adjuvant CT
NSABP-B-01  Scandinavian trial  NSABP-B-07
Bonnadonna et al [NEJM 1995]
• 386 N= pts
• Survival benefit with CMF

50. Inflammatory Breast Cancer
• Inflammatory breast cancer, as defined by the AJCC, is a composite
clinical– pathologic entity characterized by
1. Diffuse edema and erythema of the breast with acute/subacute
onset and pathologic demonstration of invasive breast cancer.
2. The erythema and skin changes must involve at least one-third of
the breast, and
3. Duration of symptoms must be <6 months.
• A critical and determinative feature of IBC is the rapid onset of
clinical findings including skin erythema, peau d’orange, brawny
breast induration, warmth, and asymmetric enlargement.

51. Inflammatory Vs Non-inflammatory Breast Cancer
Inflammatory Non-inflammatory
Dermal lymph vessel invasion is present with or
without inflammatory changes
Inflammatory changes are present without
dermal invasion
Tumor is not sharply delineated Tumor is better delineated
Erythema and Edema frequently involve
>33% of the skin over breast
Erythema is confined to the lesion , and Edema
is less extensive
Lymph node involvement is >75% of cases Lymph nodes are involved in approximately
50% of the cases
Distant metastases are present in 25% of pts Distant metastases are less common than IBC

52. Hormone therapy

54. How is ovarian ablation done ?

55. • Surgical oophorectomy
• Medical / Hormonal ablation
• Radio therapeutic ablation
How is ovarian ablation done ?
Surgical
Oophorectomy is done removing B/L ovaries and fallopian tubes either
laparoscopically or by laparotomy

56. LHRH Agonists
22.5 mg q 3 mtly
7.5 mg q 1mtly
10.8 mg 3 mtly
3.6 mg q mtly
They are used for Medical Ovarian Suppression
MOA- Desensitisation of pituitary to GnRH Secretion of LH & FSH from Pituitary

57. Radiation ablation
• Whole pelvic fields are used for
ovarian ablation.
• Dose 15 – 20 Gy is delivered
• Treatment volumes for
conventional RT-OA to extend
from the inferior border of the
fifth lumbar vertebra down to a
level traversing the middle of the
femoral heads and 1 cm lateral
to the pelvic side walls

58. Radiotherapy
• Adjuvant RT to
a) Chest Wall
b) Axilla
c) Supra clavicular fossa
d) Whole Breast in c/o BCT

60. Chest wall RT

61. Conventional field borders

62. Contouring – RTOG Guidelines

63. 3D-CRT

64. Field placements and RT planning

65. IMRT

67. • Sequential therapy is better than concurrent hormone therapy.
• The cytostatic nature of hormone therapy may interfere with the mechanism of
action and effect of chemotherapy (which is best seen in dividing cells).
• TANDEM trial –
• Result: combined treatment better.
Can we give CT and HT simultaneously
But
Anastrazole + Trastuzumab
Sequential Anastrazole

68. Molecular classification

69. Oncotype DX
• 21 Gene RT-PCR Assay [recurrence score]
• Indicated only in Early Ca Breast
1. ER/PR +ve tumors
2. Her2neu –ve tumors
3. Stage I Tumors
4. Node –ve
Group Score Treatment
Low Recurrence Group < 18 Only Adjuvant Hormone Therapy, NO CT
Intermediate Recurrence
Group
18 - 30 Only Adjuvant Hormone Therapy or
Adjuvant HT + CT
High Recurrence Group >/= 30 Both Adjuvant CT + HT
It is both Prognostic
and Predictive marker
Done on a tissue
specimen

70. Mamma Print
• It is a 70 Gene Assay test
• Indicated in
1. Stage I & II
2. Irrespective of IHC status
3. T1 and T2 lesions
4. N 0-3 +ve nodes
• Done on tissue specimen.
It is both Prognostic
and Predictive marker
Interpreted as
a. Low risk
b. High risk

71. Sequencing of Chemotherapy & Radiotherapy ?
Why ?
• No fixed protocol world wide
• Usually Chemotherapy given first because both Surgery and RT
are local treatments, systemic t/t like CT.
• But in c/o adverse risk factors after surgery RT is given first
followed by CT

72. Thank You