Clinical Case 006

(as before, answer the question is sequence fully before uncovering answers)

A 57 year old woman presents to her GP with a right breast lump and axillary lump. The GP undertakes some actions:

+ see the Bilateral mammogram

In the 12 to 1 o'clock position of the right breast approximately 2-3 cm from the nipple is an ill-defined 20 mm mass lesion associated with some pleomorphic microcalcification. The calcification extends deeper into the breast tissue posterior to the mass by a further distance of 20 mm.

+ see the Breast ultrasound following mammogram

On ultrasound the 1 o'clock right breast mammographic lesion curves onto a 20 mm ill-defined mass lesion mildly showing a hyporeflective lesion.

+ see the Core biopsy following US - histopathology report

Invasive ductal carcinoma NOS. Tumour shows diffuse strong immunoperoxidase staining for oestrogen and progesterone receptors.

Q1. Has the GP undertaken appropriate investigation?
Q2. What is the role of breast cancer tumour markers in this instance?
Q3. What features of history are relevant for future management?

The patient undergoes an operation:

Q4. What operation should be undertaken initially?

+ read the first operation report

Macroscopic:

A) RIGHT AXILLARY NODE - consists of three pieces of fibrofatty tissue 50 x 40 x 50 mm, 50 x 35 x 50 mm, 20 X 15 X 10 mm. -/7 NAE One node in each block.

B) RIGHT BREAST LUMP SHORT - SUPERIOR, LONG - LATERAL - consists of a piece of skin with nipple 83 x 47 mm. The breast tissue measures 135 mm medial to lateral, 70 mm superior to inferior, 70 mm anterior to deep. The specimen weighs 254 g. Superior inked black, deep inked blue, inferior inked red, lateral inked yellow, medial inked green. There is an ill-defined lesion measuring 20 x 20 x 15 mm behind nipple, 30 mm from anterior skin surface, 20 mm from deep margin, 50 mm from medial margin, 50 mm from lateral margin, 10 mm from superior margin, 40 mm from inferior margin. There appears to be calcification around the lesion deep into the specimen. 21/21 NAE Please see attached diagram.

Microscopic:

A) Right axillary lymph node.
All the lymph nodes present are replaced and infiltrate by metastatic carcinoma. There is marked and diffuse extranodal infiltration by the metastatic carcinoma. Extensive lymphovascular permeation and infiltration is also present.
B) Right breast lump.
Tumour - the sections show an invasive ductal carcinoma, no special type and histological grade 2 (tubules - 3, nuclear pleomorphism - 2, mitoses - 1). The main tumour is 55 mm in dimension and extends from just below the nipple to nearly 2/3 the entire anteroposterior axis of the biopsy. There are also multiple microscopic foci of invasion including within 1 mm of the inferoposterior margin deep to nipple (section (B4)) and positive lateral margin (section (B16)). Lymphovascular invasion is present.
Section (B4) posteroinferior margin - there is extensive high grade DCIS and two discrete microscopic foci of invasive ductal carcinoma both < 3mm. DCIS extends to painted margin.
Sections (B10), (B11), (B8) and (B5) - these are contiguous section from the nipple to centre of specimen deep to the nipple. All these sections show invasive ductal carcinoma and extensive high grade DCIS. Maximum tumour size from sections estimated to be 55 mm. There is also extensive lymphovascular invasion.
Sections (B15), (B16) & B(17) from lateral margin of lumpectomy show focal invasive ductal carcinoma at resection margin and high grade DCIS.
DCIS - there is approx > 30 - 35% DCIS present within tumour and extensive DCIS (> 55 mm in extent). The DCIS is solid and cribriform type with necrosis and high grade. The DCIS extends to both the posteroinferior margin deep to nipple and lateral resection margin.
Nipple - sections of the nipple show invasive ductal carcinoma in dermal plane with invasion of areola muscle.
Axillary tail - a total of three (3) plus lymph nodes are present. Metastatic carcinoma seen.
Immunohistochemistry:
Oestrogen Receptor - positive (Quirks score 8, proportion 5, intensity 3, internal and positive controls satisfactory). Progesterone Receptor - positive (Quirks score 6, proportion 4, intensity 2, internal and positive controls satisfactory).
Her2 IHC - 3+ positive (strong complete membrane staining in > 10% of cells).
Her2 ISH - positive.//

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Synoptic Report:

Specimen	Right breast lump
Tumour type	Invasive ductal carcinoma, NOS	Size: 55 mm (pT3)
		Location: 1 o'clock @ nipple margin
		Histological grade (Nottingham): 2 (tubules 2, nuclei 2, mitoses 1).
		Lymphovascular invasion: Present.
DCIS	Pattern	Solid and cribriform.
	Grade	High nuclear grade.
	Necrosis	Present.
	Percentage of DCIS in tumour	> 30 - 35%.
	DCIS in adjacent breast tissue	Extensive with positive margins both posteroinferior to nipple and lateral resection margin.
Resection margins	Closest margin	- lateral margin positive for invasive ductal carcinoma.
Calcification	Nil seen.
Nipple/skin	Invasive ductal carcinoma in deep dermal plane.
Non neoplastic breast	Extensive DCIS.
Hormone receptors	Oestrogen	Positive.
	Progesterone	Positive.
	Her2 IHC	3+ (positive).
	Her2 ISH	Positive.
Axillary lymph nodes	Number examined	Three (3) plus.
	Number involved	All involved.
	Apical node	Not sampled.
TNM	stage	pT3 pN1a(?2a) pMx

Q5. Based on this report, what are the relevant therapy decisions?
Q6. The patient (appropriately or inappropriately) returned to surgery, what operation would you advise based on the pathology report?

+ read the second operation report

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HISTOPATHOLOGY REPORT

CLINICAL NOTES:
58 YO F; R breast tumour; R mastectomy + right axillary dissection.

MACROSCOPIC:
A) APICAL LYMPH NODE RIGHT AXILLA - consists of two pieces of fibrofatty tissue, 25 x 10 x 8 mm and 40 x 30 x 15 mm. Two probable lymph nodes found.
Block legend: (1) one lymph node bisected (2) ? two lymph nodes bisected. 4/2 PE
B) RIGHT BREAST - consists of an ellipse of skin 140 x 55 mm with underlying fibro-fatty breast tissue 140 x 100 x 60 mm. The skin contains a central linear scar 8 x 2 mm. The specimen weighs 425 g. It is not orientated. Deep surface inked black, other margins inked blue. On slicing, there is a cavity 20 x 20 x 60 mm, 10 mm from the skin surface and 30 mm from the deep margin. The wall of the cavity is firm and pink in colour. The cavity contains sero-sanguineous fluid. The cut surface away from the cavity shows fibrofatty tissue, no focal lesion is seen.
Block legend: (1&2) TS from each end of cavity (3,4,5&6)
complete cavity section (7.8.9&10) complete cavity section (11,12,13&14) complete cavity section. 14/14 PE
C) RIGHT AXILLARY CLEARANCE - consists of a piece of fibro-fatty tissue 70 x 40 x 25 mm. The specimen is serially sliced and has a fibrofatty cut surface. Three lymph nodes were found.
Block legend: (1) two lymph nodes (2) one lymph node bisected. 4/2 PE WO/mm 26.05.08

MICROSCOPIC:
A) Sections show a lymph node extensively infiltrated by metastatic ductal carcinoma with multifocal extra nodal extension, up to 0.6 mm. The tissue also shows multiple deposits of carcinoma adjacent to lymphatics containing tumour. These deposits of cancer are up to 3.5 mm.
B) Sections of the mastectomy specimen show residual grade 2 invasive ductal carcinoma NOS (tubule formation 3, nuclear pleomorphism 2, mitotic index 2) adjacent to the surgical cavity and extending up to 8 mm into the breast tissue, lateral and superficial to the surgical cavity. There is associated intermediate grade, cribriform and solid ductal carcinoma in-situ that focally shows dystrophic calcification. There is extensive lymphatic space invasion and dermal lymphatics contain tumour in several sections of the skin. Ductal carcinoma in-situ is 12 mm from the nearest surgical margin. Invasive carcinoma is at least 25 mm from the closest (deep) surgical margin.
C) Sections show two lymph nodes, one of which is extensively infiltrated by invasive ductal carcinoma NOS. There is no extra nodal extension. However, there is a separate deposit of invasive carcinoma 7 mm across.

SUMMARY:
A) Apical lymph node right axilla - METASTATIC INVASIVE DUCTAL CARCINOMA NOS WITH EXTRA NODAL EXTENSION.
B) Right breast (mastectomy) - RESIDUAL GRADE 2 INVASIVE DUCTAL CARCINOMA NOS.
C) Right axillary clearance - ONE OF TWO LYMPH NODES EXTENSIVELY INFILTRATED BY METASTATIC DUCTAL CARCINOMA. DEPOSIT OF INVASIVE CARCINOMA, 7 MM ACROSS.

Q7. What do you believe are the risks for locoregional and distant failure in this patient?
Q8. Discuss the evidence that radiotherapy improves survival in breast cancer.
Q9. List the treatments required with justification. Also provide the specific details of all these therapies you list.
Q10. Table the local, regional & distant recurrence rates before the treatment you specify, and the rates with the treatment package you specify.
Q11. Table the major side effects (with rates) for all the treatments you describe.