Occult breast primary

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Case Presentation

HPI

● Pt is a 58 y.o. female with a history of atypical ductal hyperplasia on a core needle biopsy and
excisional biopsy in 2016.

● Prophylactic antihormonal therapy was discussed with patient at that time and declined
treatment.

● She presents for evaluation of a right breast tender mass for approximately 1 month on
9/24/21.

● PMH: Abnormal Pap smear.

● PSH: Tubal ligation; Breast biopsy (Right, 09/2016); Breast surgery (Right, 12/14/2016)

● Family Hx: ? Cancer in her maternal grandmother and paternal aunt.


HPI

Hormonal risk factors for breast cancer:

Menarche at age 14
First full term pregnancy at age 24
Menopause at age 51
No hormonal replacement therapy

Physical exam:

Right: 5 cm Mass at R breast axillary tail, TTP. No swelling, bleeding, inverted nipple, nipple
discharge, skin change, axillary adenopathy or supraclavicular adenopathy.

Left: Tenderness present. No swelling, bleeding, inverted nipple, mass, nipple discharge, skin
change, axillary adenopathy or supraclavicular adenopathy.
Clinical course
1)Screening mammogram 6/8/2016 at Main Street Radiology BI-RADS 0

2) Bilateral screening mammogram 9/1/2021 at Main Street radiology BI-RADS R4 L2

3) Bilateral breast ultrasound 9/1/2021 at Main Street radiology BI-RADS R4 L3 (10:00 location, 9 cm
from the nipple, 4.4 cm hypoechoic mass).

4) S/P right lymph node guided core biopsy by flushing IR 1/6/2022

LYMPH NODE/BREAST, RIGHT AXILLA, BIOPSY:


- POORLY DIFFERENTIATED CARCINOMA IN A BACKGROUND OF ABUNDANT LYMPHOID
TISSUE, PROBABLY METASTATIC (SEE COMMENT)

Immunohistochemical stain are positive for CK 7 and GATA3, all other


markers are negative. no evidence of a B-cell or T-cell lymphoma. ER negative (less than 1%) PR
negative (0%) HER-2 negative
Pathology
Clinical course

6) Bilateral breast MRI 1/27/2022 at Main Street radiology BI-RADS R4 (2 cm area of branching
non-mass enhancement at the 3 o'clock position, 4 cm from the nipple)
7) MRI guided right breast biopsy 2/8/2022 at Main Street radiology: (Large intraductal papilloma
incompletely removed).
8) S/P right breast needle localized excisional biopsy 3/23/2022
DIAGNOSIS:
BREAST, RIGHT, EXCISION:
- DUCTAL CARCINOMA IN SITU, CRIBRIFORM, NUCLEAR GRADE 1 TO 2, FOCAL
NECROSIS (0.4 CM).
- MICROCALCIFICATIONS ASSOCIATED WITH DCIS.
9) Clinical staging at this time T0N1M0 , currently patient is scheduled for PET, Medical oncology follow
up and genetic testing.
Management of Occult Breast
CA with Axillary Metastasis
Outline
Introduction
Imaging
Value of GATA-3
Treatment of occult primary breast CA with isolated axillary metastasis
Prognosis of occult primary breast Ca presenting with isolated axillary metastasis
Summary
Introduction
● Malignancy is diagnosed in 20% of those with persistent lymphadenopathy.

● Most common is axillary lymphadenopathy, greater than 50% of it primary originates from
the breast. Commonly a breast lesion is identified, but on occasion no primary is found.

● This is termed occult breast cancer (OBC) and was first described in 1907 as “cancerous
axillary glands with non-demonstrable cancer of the mamma”. Initially, OBC was defined by
the absence of an in-breast clinical finding alone but the definition has broadened to also
include negative mammography and ultrasonography.

● The incidence of the latter is reported as being 0.3–1% of all breast cancer patients. It is
thought that OBC is secondary to micro-invasive breast cancer.

Breast. 2020;54:211-215. doi:10.1016/j.breast.2020.10.012


Imaging

● The American College of Radiology recommends the use of MRI for OBC patients that do
not have evidence of a breast primary on traditional radiological examination
(mammogram and ultrasound) and clinical exam.

● Level I evidence has shown MRI is significantly more sensitive in detecting a primary
lesion that mammography or ultrasound; identifying a primary in 72% of cases that were
deemed occult.

● Currently, 3.0 T (T) breast MRIs have demonstrated greater spatial resolution and
improved signal to noise ratio, compared to earlier 1–1.5T MRIs. This has resulted in
improved detection and a better positive predictive value

Breast. 2020;54:211-215. doi:10.1016/j.breast.2020.10.012


● 40 pts with biopsy-proven metastatic adenocarcinoma to an axillary lymph node and no evidence of
primary cancer were studied.

● Positive MRI scans were compared with histopathologic findings at the time of operation (n = 21).

● MRI identified the primary breast lesion in 28 of 40 women (70%).

● Of these 28 patients, 11 had MRM, 11 had lumpectomy/axillary lymph node dissection


(ALND)/radiotherapy (XRT), 2 had ALND/XRT alone, and 4 had no local treatment secondary to stage IV
disease. Two women initially treated with lumpectomy/ALND subsequently had mastectomy for positive
margins.

● Of the women with positive MRI who had breast surgery, 21 of 22 (95%) had tumor within the surgical
specimen.
Ann Surg Oncol. 2000 Jul;7(6):411-5. doi:10.1007/s10434-000-0411-4.
● Twelve women had negative MRI of the breast. Five of these 12 underwent MRM, of whom 4 had no tumor in
the mastectomy specimen. The remaining 7 patients had ALND and whole breast radiation (ALND/XRT) (n = 5),
or were observed (n = 2). Overall, 18 of 34 women surgically treated had MRM, while 16 (47%) preserved their
breast. Tumor yield for patients having breast surgery was 81%.

● Concluded that MRI of the breast can identify occult breast cancer in many patients and may facilitate breast
conservation in select women. Negative breast MRI predicts low tumor yield at mastectomy.

Ann Surg Oncol. 2000 Jul;7(6):411-5. doi:10.1007/s10434-000-0411-4.


Imaging

● Positron emission mammography (PEM) is a newly emerging investigatory tool which uses FDG to
localise smaller tumours especially those less than 1 cm and has a greater sensitivity than PET/CT in
this subset of patients with small tumours.

● A randomized multicentre study by Berg et al. (2011) compared PEM to MRI in 388 newly diagnosed
breast cancer patients. Though PEM had higher specificity (91.2% vs 86.3%), MRI showed greater
sensitivity in detecting additional cancers (53% vs 41%).

Breast. 2020;54:211-215. doi:10.1016/j.breast.2020.10.012


● This meta-analysis of 10 articles involving 5,080 breast cancer patients explored the prognostic and
clinicopathological value of GATA3 in breast cancer.

● Time to tumor progression (TTP) and overall survival (OS) were primary endpoints. Pooled hazard ratio (HR),
pooled risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate the association between
GATA3, prognosis, and clinicopathological parameters.

● High GATA3 expression predicts breast cancer, with a HR (HR = 0.671; 95% CI = 0.475-0.947; P = 0.023) of TTP,
but is not associated with OS (HR = 0.889; 95% CI = 0.789-1.001; P = 0.052).

PLoS One. 2017 Apr 10;12(4):e0174843. doi: 10.1371/journal.pone.0174843. eCollection 2017


● GATA3 overexpression is associated with positive ER (RR = 3.155; 95% CI = 1.680-5.923; P =

0.000), positive PR (RR = 3.949; 95% CI = 1.567-9.954, P = 0.004), lower nuclear grade (RR =

0.435; 95% CI = 0.369-0.514; P = 0.000), and smaller tumor size (RR = 0.816; 95% CI =

0.709-0.940; P = 0.005).

● High GATA3 expression may predict TTP in breast cancer, and such patients may show

better clinicopathological features.

PLoS One. 2017 Apr 10;12(4):e0174843. doi: 10.1371/journal.pone.0174843. eCollection 2017


Treatment of occult primary breast CA with isolated axillary metastasis
(NCCN GUIDELINES)

● MRI positive breast disease should undergo evaluation with ultrasound or MRI guided biopsy
and receive treatment according to the clinical stage of the breast cancer.

● Treatment recommendation for those with MRI-negative disease are based on nodal status.

● For patients with T0N1M0 options include mastectomy plus axillary nodal dissection or
ALND w/ WBRT w/ or w/o nodal irradiation.

● Systemic chemotherapy, endocrine therapy or trastuzumab is given according to


recommendations for stage II or Stage III.

● Neoadjuvant chemotherapy, trastuzumab, and endocrine therapy should be considered


for patients with T0N2-3M0 followed by ALND and mastectomy as for patients with locally
advanced disease.
Prognosis of occult primary breast Ca presenting with isolated axillary metastasis

● Retrospective review of patients who presented with axillary nodal metastases from an occult breast carcinoma
between 1997 and 2004 at the Roswell Park Cancer Institute

● 2,150 patients were diagnosed and treated for breast cancer during this period. After excluding stage I and IV
patients, 642 who had disease metastatic to lymph nodes, 10 of these had no primary tumor in the breast
despite a thorough evaluation including bilateral mammography and breast ultrasound.

● Of these, 7 had undergone breast magnetic resonance imaging as well. All patients underwent axillary nodal
dissection. The breast was managed with radiotherapy alone in 8 patients, wide local excision with radiation
therapy in 1 patient and 1 patient underwent mastectomy.

● No patient had a recurrence with a median 57 months of follow-up.

● Breast conservation with radiation therapy alone can be considered as a management option for women
with occult breast cancer presenting with axillary nodal metastasis.

Oncology2006;71(5-6):456-9. doi: 10.1159/000107111. Epub 2007 Aug 9.


Summary
Occult breast cancer with metastasis to the axilla is considered probably from microinvasive,
incidence to 0.3-1% of all breast CA.

MRI plays a vital role in identifying the primary lesion in most of the clinically occult and
negative US/Mammogram

Evidence to date suggests that better outcomes are achieved if the ipsilateral breast is treated
and given the equivalent outcomes for whole breast radiation versus surgery, patients can
safely avoid mastectomy.
Reference

1. Ofri A, Moore K. Occult breast cancer: Where are we at?. Breast. 2020;54:211-215. doi:10.1016/j.breast.2020.10.012

2. Olson, J.A., Morris, E.A., Zee, K.J.V. et al. Magnetic Resonance Imaging Facilitates Breast Conservation for Occult Breast
Cancer. Ann Surg Oncol 7, 411–415 (2000). https://doi.org/10.1007/s10434-000-0411-4.

3.Guo Y, Yu P, Liu Z, Maimaiti Y, Chen C, Zhang Y, Yin X, Wang S, Liu C, Huang T. Prognostic and clinicopathological value of
GATA binding protein 3 in breast cancer: A systematic review and meta-analysis. PLoS One. 2017 Apr 10;12(4):e0174843. doi:
10.1371/journal.pone.0174843. PMID: 28394898; PMCID: PMC5386271.

4. Varadarajan R, Edge SB, Yu J, Watroba N, Janarthanan BR. Prognosis of occult breast carcinoma presenting as isolated
axillary nodal metastasis. Oncology. 2006;71(5-6):456-9. doi: 10.1159/000107111. Epub 2007 Aug 9. PMID: 17690561.

5. NCCN Occult breast CA with axillary metastasis guidelines

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