Running head: MEDICAL CASE ANALYSIS 1

Breast Malignancy Medical Review

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Breast Malignancy Medical Review

Regular Mammography represents the best method of screening for breast malignancy but

the diagnosis needs to be confirmed through needle biopsy

The principles of mammography will involve breast imaging that uses low-dose x-rays to

detect suspicious mass and cancer in early stages. The basic principle of mammography is based

on the x-rays that penetrate the tissue and get captured on a film plate located in the opposite

position. Even though calcifications are frequently associated with noncancerous tumors, they

are presented in irregular clusters in the case of Diana, demonstrating the need for further

investigations such as needle biopsy.. Diana's histological sample points out a diagnosis of

invasive ductal carcinoma. The sample presents a variable level of necrosis, poorly differentiated

cells that tend to be pleomorphic. Nevertheless, the invasion of the basement membrane is also

visible, further confirming the diagnosis. Even though the needle biopsy technique tends to be

rapid and simple, it provides only a cytological evaluation, which is not enough to propose a

clear treatment. It also leads to a loss of tissue architecture, making it hard to differentiate an

invasive carcinoma from an in situ one.

The most diagnosed histological type is the invasive ductal carcinoma

Histological subtype is essential to determine the risk of metastasis and the most

approachable treatment plan. Classifying the tumor from a histological perspective is essential as

it provides the clinician with the right information to predict the prognosis of the patient and the

most suitable treatment. Even so, there exist limitations for this step too. Usually, it is required

to conduct complementary examinations such as the grading of the cells to provide further

information that will allow the classification of the patient in prognostic subgroups. The two

subtypes which are commonly identified are represented by Invasive Ductal Carcinoma (IDC)

and Invasive Lobular Carcinoma (ILC). For example, histological examinations can point out
 MEDICAL CASE ANALYSIS 3

that ILC tends to have a worse prognosis than IDC, which leads to various clinical trials focusing

on this subgroup of patients. (Meattini et al., 2019). For the case study involving Diana,

analyzing her histological tumor subtype can help identify the tumor’s behavior to her body and

analyze the possible treatment choice. When it comes to the IDC, it is not only the most common

histological type but also the one with the highest risk of metastasis through lymphatics. The

most characteristics aspect is represented by an invasion of the basement membrane (Pop et al.,

2018). Even though the result will require both clinical and imaging integration, histopathology

represents without any doubts an essential step in evaluating the surgical and oncological

therapies options for the patient in cause. Figure 1 points towards the IDC characteristics in

Diana’s sample. (Takahashi et al., 2020).

Figure 1: The red arrow points towards tumoral cells infiltration while the black arrow towards

areas of comedo necrosis. Other elements visible in this sample are represented by the ectasia of the

breast ducts, including fibrocystic modifications. All these are suggestive for a histological diagnosis of

invasive ductal carcinoma.

The lack of molecular characteristics of histological analysis limits its prognostic value.
 MEDICAL CASE ANALYSIS 4

As the course lectures were able to point out, histological subtype alone is not enough to

predict treatment's possible response. Thus, further examinations such as molecular profiling are

essential as it characterizes the tumor based on gene expression. The immunohistochemistry

elements which are frequently examined include the hormone receptors, the triple-negative/basal

like factor, HER2, and other prognostic markers such as Ki57 or E-cadherin. Determining the

endocrine sensitivity is essential in Diana's case as it can point out various forms of therapies that

can be effective (such as tamoxifen, anastrozole, leuprolide or fulvestrant).

Figure 2: The ki-67 positive cancer cells are stained in brown, as demonstrated by the red circles. As the

results were able to point out, while calculating this through the ImageJ application, it was evident that it

exceeds 20% of the sample's cells, meaning that the tumor has a high division rate. In order to confirm

the result, 4 samples from the patients tumoral mass were analyzed through the software, all pointing out

an average of 70-80% positive cells.

Figure 3: Picture A) features the estrogen receptors staining with a value of approximately 10% of total

cells, being classified with a score of 2. Picture B) features the HER2 staining with a score of 2, meaning

no more than 10% of tumor cells ,Picture C) features the progesterone receptors in the box with a value

of <1% nuclei staining, classified as score 1.

Based on all this analysis, it would be stated that the patient has a high value of ki67, low

for hormone receptors as progesterone showed a score of 1 while the estrogen was slightly

higher with a value of 2, and medium for HER2 (equaling a score of 2). Despite the low

expression, Diana’s case is still positive for hormone receptors. All of these are annotated in

figure 3. Based on that, the molecular subclassification will point towards a Luminal B form,

which has a prevalence of 10-24%.

Gradation points out how abnormal the cells are and how advanced the disease is.
 MEDICAL CASE ANALYSIS 6

Figure 4: Picture A) points out a presence of less than 10% of tubule formation, meaning a score of 3,

Picture B) points out marked variation in terms of nuclear appearance, meaning a score of 3, while

Picture C) depicts A mitotic count of over 15 meaning a score of 3.

Tumor gradation involves the evaluation of cancer cell reflecting their normal or

abnormality when compared to the standard breast cells and tissues. For Diana's case, three

elements will be considered: tubule formation, nuclear pleomorphism, and mitotic count as

considered in figure 4 All of these factors seem to be excessively modified, which means that

she would be classified in a grade 3 breast cancer due to the fact that she has a final score of 9

based on the three elements considered. There are marked variations in terms of nuclear

pleomorphism, tubular structures are modified compared to the physiological ones, and the

mitotic count is increased. In conclusion, the architectural pattern and structures are no longer

maintain, and Diana has a poorly differentiated form of malignancy.

The AJCC recommends the anatomical classification of the disease based on the TNM

protocol.
 MEDICAL CASE ANALYSIS 7

For Diana, the tumor has a size of 1.7 cm meaning that it is classified as T1C. Even

though five lymph nodes were removed, only the sentinel one was affected, meaning that this

would be classified as N1. the CT scan indicates the presence of a mass in the right lung. This

could not be related to her COPD as that disease presents on the CT with forms of emphysema

and chronic bronchitis (thickening of the bronchial wall). In the given circumstances, it would

be efficient to conduct a biopsy of the mass to determine if the lesion is related to the

malignancy. If it is confirmed, that would mean that the M value would be 1; otherwise, it would

be 0. Finding out the origin of the lung lesion is very important as it has a massive effect on the

prognosis of the patient. In case the lesion is malignant, the patient would be classified in stage

IV of breast cancer. In the opposite situation, she would be classified in stage II. The exact

classification of the patient is depicted in figure 5.As it can be seen, Diana is dealing with a

systemic case.

The size of the tumor is equal to 1.7 cm which means it can be

Five lymph nodes were removed, but only the sentinel one
presented malignancy cells.
N1
The patient presents a lung mass, which can represent the first sign
of metastasis. Due to that, her pathology is classified as a systemic
M1 one.

Figure 5: A chart aimed to present in an easier manner the staging for Diana’s case

accordingly to the TNM system

If it is confirmed malignant, the survival rate would drop to only 15% as metastasis

represents one of the worst prognosis elements with only a few effective treatment options.

(Alkabban,2019) Based on in depth analysis, through FISH analysis, the sample pointed out no

mutations while the BRCA testing was negative too. In the given scenario, this would mean that

Diana is not a carrier of the gene which would further conclude that this is a situation not related

to family history. Usually this gene is assessed to determine the risk of the patient to develop

breast malignancy across their lifespan. (Casaubon et al,2020).

There are three major classes of therapy: surgery, chemotherapy and radiotherapy.

As the analysis was able to point out, Luminal B cancer tends to be hormone receptor-

positive, HER 2 positive, and with a high value of Ki-67. Due to that, the prognosis tends to be

slightly worse when compared to the other forms due to the fact that it can grow faster. Due to all

this information, the patient is eligible for hormonal therapy. Diana could benefit from all the

forms of therapy, which include surgical removal of the mass, chemotherapy, and radiation.

After that, care providers can provide adjuvant therapy consisting of hormonal treatment to

reduce recurrence risk. Administration of medication such as Trastuzumab or pertuzumab can be

efficient due to the fact that the samples point out that this is a Her 2 positive malignancy. Most

frequently, both HER2 targeted medication and chemotherapy are provided before the surgical

resection to reduce the size of the tumor and the risk of dissemination. Chemotherapy tends to be

administered as soon as possible, and the duration can last for up to 6 months or even longer if it

is the case. Usually, the staging and risk of dissemination will determine the length of

chemotherapy. (Dittmer, 2018).

Many clinical trials focus on the molecular characteristics in order to increase the

survivability rate especially for the advanced diseases.

In the situation in which the patient would be confirmed with metastatic lung pathology,

she could join a phase III trial study which tries to determine if administration of

pertuzumab,trastuzumab, and paclitaxel together with atezolizumab could reduce the

dissemination risk. Diana would be eligible for this trial because of the possibility of lung

metastasis and the fact that the tumor specimen is HER2 positive as depicted in figure 6. The

overall purpose of this clinical trial is to determine if adding atezolizumab (monoclonal

antibody) to the therapy would be efficient in increasing the life expectancy of these patients.

(NIH,2020)

Figure 6: The graphic represents the two drugs' method of action in the clinical trial:

pertuzumab and trastuzumab. As shown, trastuzumab will find to the ECD IV at the level of the

receptor HER 2. On the other hand, pertuzumab will bind to the ECD II location and prevent

heterodimerization.

Besides, due to the fact that she has a high-grade tumor, she could also join a clinical trial

aiming to determine if trastuzumab, when combined with tucatinib, might be able to prevent

relapses, especially in patients with HER2 positive malignancies. The researchers desire to

determine if patients who receive these two drugs tend to have a lower chance of relapses than

those who receive only the monoclonal antibody trastuzumab. (NIH,2020)

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